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Dossier for Candidate Low-Priority Substance Tetracosane,
2,6,10,15,19,23-hexamethyl-
(CASRN 111-01-3)
(Squalane)
For Release at Proposal
August 9, 2019
Office of Pollution Prevention and Toxics
U.S. Environmental Protection Agency
1200 Pennsylvania Avenue
Washington, DC 20460
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Contents
1. Introduction 1
2. Background on Squalane 3
3. Physical-Chemical Properties 4
3.1 References 6
4. Relevant Assessment History 7
5. Conditions of Use 8
6. Hazard Characterization 12
6.1 Human Health Hazard 15
6.1.1 Absorption, Distribution, Metabolism, Excretion 15
6.1.2 Acute Toxicity 16
6.1.3 Repeated Dose Toxicity 16
6.1.4 Reproductive and Developmental Toxicity 17
6.1.5 Genotoxicity 17
6.1.6 Carcinogenicity 17
6.1.7 Neurotoxicity 18
6.1.8 Skin Sensitization 18
6.1.9 Skin Irritation 18
6.1.10 Eye Irritation 18
6.1.11 Hazards to Potentially Exposed or Susceptible Subpopulations 18
6.2 Environmental Hazard 19
6.2.1 Acute Aquatic Toxicity 19
6.2.2 Chronic Aquatic Toxicity 19
6.3 Persistence and Bioaccumulation Potential 19
6.3.1 Persistence 19
6.3.2 Bioaccumulation Potential 20
7. Exposure Characterization 20
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7.1 Production Volume Information 20
7.2 Exposures to the Environment 21
7.3 Exposures to the General Population 21
7.4 Exposures to Potentially Exposed or Susceptible Subpopulations 21
7.4.1 Exposures to Workers 21
7.4.2 Exposures to Consumers 22
8. Summary of Findings 23
8.1 Hazard and Exposure Potential of the Chemical Substance 23
8.2 Persistence and Bioaccumulation 24
8.3 Potentially Exposed or Susceptible Subpopulations 24
8.4 Storage Near Significant Sources of Drinking Water 25
8.5 Conditions of Use or Significant Changes in Conditions of Use of the Chemical Substance 26
8.6 The Volume or Significant Changes in Volume of the Chemical Substance Manufactured or Processed.... 26
8.7 Other Considerations 27
9. Proposed Designation 28
Appendix A: Conditions of Use Characterization I
A.1 CDR Manufacturers and Production Volume I
A.2 Uses II
A.2.1 Methods for Uses Table II
A.2.2 Uses of Squalane IV
A.3 References XIII
Appendix B: Hazard Characterization XVII
B.1 References XXIX
Appendix C: Literature Search Outcomes XXXII
C.1 Literature Search and Review XXXII
C.1.1 Search Terms and Results XXXIII
C.2 Excluded Studies and Rationale XXXVIII
C.2.1 Human Health Hazard Excluded References XXXVIII
C.2.2 Environmental Hazard XLIII
C.2.3 Fate XLVI
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Tables
Table 1: Squalane at a Glance 3
Table 2: Physical-Chemical Properties for Squalane 4
Table 3: Conditions of Use for Squalane 9
Table 4: Low-Concern Criteria for Human Health and Environmental Fate and Effects 12
Table A.1:1986-2015 National Production Volume Data for Squalane (Non-Confidential Production I
Volume in Pounds)
Table A.2: Sources Searched for Uses of Squalane II
Table A.3: Uses of Squalane IV
Table B.1: Human Health Hazard XVII
Table B.2: Environmental Hazard XXIV
Table B.3: Fate XXV
Table C.1: Search Terms Used in Peer-Reviewed Databases XXXIII
Table C.2: Search Terms Used in Grey Literature and Additional Sources XXXVII
Table C.3: Off-Topic References Excluded at Title/Abstract Screening for Human Health Hazard XXXIX
Table C.4: Screening Questions and Off-Topic References Excluded at Full-Text Screening for Human XXXIX
Health Hazard
Table C.5: Data Quality Metrics and Unacceptable References Excluded at Data Quality Evaluation for XLI
Human Health Hazard - Animal
Table C.6: Off-Topic References Excluded at Title/Abstract Screening for Environmental Hazard XLIII
Table C.7: Screening Questions and Off-Topic References Excluded at Full-Text Screening for XLIV
Environmental Hazard
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Table C.8: Data Quality Metrics and Unacceptable References Excluded at Data Quality Evaluation for XLV
Environmental Hazard
Table C.9: Off-Topic References Excluded at Initial Screening for Fate XLVI
Table C.10: Screening Questions and Off-Topic References Excluded at Full-Text Screening for Fate XLVII
Table C.11: Data Quality Metrics and Unacceptable References Excluded at Data Quality Evaluation for XLVI 11
Fate
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1. Introduction
In the Lautenberg amendments to the Toxic Substances Control Act (TSCA) (section 6(b)(1)(B)) and
implementing regulations (40 CFR 702.3), a low-priority substance is described as a chemical
substance that the Administrator concludes does not meet the statutory criteria for designation as a
high-priority substance, based on information sufficient to establish that conclusion, without
consideration of costs or other non-risk factors. A high-priority substance is defined as a chemical
substance that the Administrator concludes, without consideration of costs or other non-risk factors,
may present an unreasonable risk of injury to health or the environment because of a potential hazard
and a potential route of exposure under the conditions of use, including an unreasonable risk to
potentially exposed or susceptible subpopulations identified as relevant by the Administrator.
Tetracosane, 2,6,10,15,19,23-hexamethyl-, referenced as squalene for the remainder of this document,
is one of the 40 chemical substances initiated for prioritization as referenced in a March 21, 2019
notice (84 FR 10491). 1
Before determining low or high prioritization status, under EPA's regulations at 40 CFR 702.92 and
pursuant to section 6(b)(1)(A) of the statute, EPA will generally use reasonably available information
to screen the candidate chemical substance under its conditions of use against the following criteria
and considerations:
• the hazard and exposure potential of the chemical substance;
• persistence and bioaccumulation;
• potentially exposed or susceptible subpopulations;
• storage near significant sources of drinking water;
• conditions of use or significant changes in the conditions of use of the chemical substance;
• the chemical substance's production volume or significant changes in production volume; and
• other risk-based criteria that EPA determines to be relevant to the designation of the chemical
substance's priority.
Designation of a low-priority substance indicates that the chemical substance does not meet the
statutory criteria for a high-priority substance and that a risk evaluation is not warranted at the time.
This risk-based, screening-level review is organized as follows:
• Section 1 (Introduction): This section explains the requirements of the Lautenberg
amendments to the Toxic Substances Control Act (TSCA) and implementing regulations -
including the criteria and considerations ~ pertinent to prioritization and designation of low-
priority substances.
1 https://www.federalregister.gov/documents/2019/03/21/2019-054Q4/initiation-of-prioritization-under-tlie-toxic-substances-
control-act-tsca
2 Hie prioritization process is explained in the Procedures for Prioritization of Chemicals for Risk Evaluation Under the
Toxic Substances Control Act (82 ER 33753).
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• Section 2 (Background on the Proposed Low-Priority Substance): This section includes
information on attributes of the chemical substance, including its structure, and relates them
to its functionality.
• Section 3 (Physical-Chemical Properties): This section includes a description of the physical-
chemical properties of the chemical substance and explains how these properties lead to the
chemical's fate, transport, and exposure potential.
• Section 4 (Relevant Assessment History): This section includes an overview of the outcomes
of other governing entities" assessments of the chemical substance.
• Section 5 (Conditions of Use): This section presents the chemical substance's known,
intended, and reasonably foreseen conditions of use under TSCA.
• Section 6 (Hazard Characterization): This section summarizes the reasonably available
hazard information and benchmarks the information against low-concern thresholds.
• Section 7 (Exposure Characterization): This section includes a qualitative summary of
potential exposures to the chemical substance.
• Section 8 (Summary of Findings): In this section, EPA presents information pertinent to
prioritization against each of the seven statutory and regulatory criteria and considerations,
and proposes a conclusion based on that evidence.
• Section 9 (ProposedDesignation): In this section, EPA presents the proposed designation for
this chemical substance.
• Appendix A (Conditions of Use Characterization): This appendix contains a comprehensive
list of TSCA and non-TSCA uses for the chemical substance from publicly available
databases.
• Appendix B (Hazard Characterization): This appendix contains information on each of the
studies used to support the hazard evaluation of the chemical substance.
• Appendix C (Literature Search Outcomes): This appendix includes literature search outcomes
and rationales for studies that were identified in initial literature screening but were found to
be off-topic or unacceptable for use in the screening-level review.
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2. Background on Squalane
Table 1 below provides the CAS number, synonyms, and other information on squalane.
Table 1: Squalane at a Glance
Chemical Name
Squalane
CASRN
111-01-3
Synonyms
Tetracosane, 2,6,10,15,19,23-hexamethyl-; 2,6,10,15,19,23-Hexamethyltetracosane;
Hexamethyl tetracosane; Tetracosane,6,10,15,19,23-hexamethyl-; Squalane
(Polyquaternium-39); Cosbiol; Perhydrosqualene; Dodecahydrosqualene
Trade Name(s)
Evoil; Neossance; Robane; Spinacane, Vitabiosol
Molecular Formula
C30H62
Representative Structure
Squalane is a saturated hydrocarbon oil that is formed by the hydrogenation of squalene. Its structure
is composed of a 24-carbon chain substituted with six methyl groups in the 2, 6, 10, 15, 19, and 23
positions. Squalane can be found in small quantities in sebum, a natural substance that acts as an
antioxidant and protects the skin from bacteria while keeping it hydrated. Squalene is most commonly
found in nature as a lipid in both plants and animals, most notably in shark livers, olive oil, rice, and
sugar cane. Section 5 includes conditions of use for this chemical.
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3. Physical-Chemical Properties
Table 2 lists the physical-chemical properties for squalane. A chemical's physical-chemical properties provide a basis for understanding a
chemical's behavior, including in the environment and in living organisms. These endpoints provide information generally needed to assess
potential environmental release, exposure, and partitioning as well as insight into the potential for adverse toxicological effects.
Table 2: Physical-Chemical Properties for Squalane
Source/
Model
Data Type
Endpoint
Endpoint value
Notes
Sigma-Aldrich 2019
Experimental
Physical state at
room temp
(based on melting
point)
Liquid (-38°C)
ECHA 2018
Experimental
Molecular weight
423 g/mol
EPISuite v.4.113
Calculated
Molecular weight
422.83 g/mol
Lyman etal. 1990
Experimental
Molar volume
673.4 cm3/mol
LeBas Molar Volume, calculated according to the volume parameters
reported in Lyman et al., 1990
EPISuite v.4.11
Estimated
Water solubility
<1E-8 mg/L
ECHA 2018
Experimental
Water solubility
1.42x10-5 mol/L;
2.37x10-6 mol/L;
7.10x10"6 mol/L
ECHA 2018
Experimental
Log Kow
5.49 at 20 deg C and
pH 6.4
The measured octanol-water partition coefficient is most likely
underestimated by the test method (OECD 107). Study authors noted that
squalane is completely soluble in octanol (> 10,000 g/L), but that in water,
the chemical is very weakly soluble and that the solubility is under the
detection limit.
EPISuite v.4.11
Estimated
Log Kow
>8
EPISuite v.4.11
Estimated
Log Koa
9.83
EPISuite v.4.11
Estimated
Log Koc
8.0 (MCI); 12.7 (Kow)
ECHA 2018
Experimental
Vapor pressure
3.6x10"10 mm Hg
(4.8X10-8 Pa at 20°C)
EPISuite v.4.11
Estimated
Vapor pressure
2.75x10"4 mm Hg
3 EPI Suite (Physical Property Inputs - BP = 350°C, MP = -38°C), SMILES: CC(C)CCCC(C)CCCC(C)CCCCC(C)CCCC(C)CCCC(C)C
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Table 2: Physical-Chemical Properties for Squalane
Source/
Model
Data Type
Endpoint
Endpoint value
Notes
EPISuite v.4.11
Estimated
Henry's Law
1500 atm-m3/mole
EPISuite v.4.11
Estimated
Volatilization
2.1 hours (river)
195 hours (lake)
EPISuite v.4.11
Estimated
Photolysis
(indirect)
3.17 hours (T1/2)
• OH rate constant 4.05E-11 cm3/molecules-second (12-hour day; 1.5E6
OH/cm3)
• No ozone reaction estimation
Ruehl et al. 2013
Esimtated based
on experimental
data
Photooxidation
(T1/2)
6.7 days
• Hydroxyl radical decay rate constant = 1,6±0.4E-12 cm3/molecules-
second (12-hour day; 1.5E6 OH/cm3)
EPISuite v.4.11
Estimated
Hydrolysis
Rate constants
cannot be estimated
No hydrolyzable functional groups
EPISuite v.4.11
Estimated
Biodegradation
potential
Ready prediction: No
EPISuite v.4.11
Estimated
BAF
7.7
EPISuite v.4.11
Estimated
BCF
3.2
Based on regression equation
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EPA's Sustainable Futures/P2 Framework Manual4 was used to interpret the physical-chemical
properties provided in Table 2. Based on its reported physical state and melting point, squalane is a
liquid at ambient temperatures. Liquids have the potential for exposure via direct dermal contact with
the substance, ingestion, and by inhalation of aerosols, if they are generated. Based on its
experimental vapor pressure (ECHA, 2018), squalane is not volatile under ambient conditions,
minimizing the potential for exposure through inhalation of vapors. Further, if aerosols are generated,
absorption across the lungs is unlikely. Based on its estimated water solubility, squalane is insoluble
in water (ECHA, 2018). Given its low water solubility, this chemical is unlikely to be absorbed
dermally or from the gastrointestinal tract. The estimated log K0„ indicates that squalane is not likely
to be bioavailable, and it has low potential for absorption and sequestration in fatty tissue, as
confirmed by its estimated bioconcentration factor (BCF) and bioaccumulation factor (BAF)
(EPISuite v4.11). Squalane"s estimated log Koc indicates squalane is likely to adsorb to sediment and
soil particles (EPISuite v4.11). It is predicted to be immobile in soil, which along with its water
insolubility, shows a decreased potential to contaminate groundwater, including well water.
Experimental biodegradation data indicate that squalane is biodegradable in aerobic conditions
(discussed further in Section 6.3.1), meaning this chemical is not persistent and it has the potential to
be broken down into carbon dioxide and water.
3.1 References
European Chemicals Agency (ECHA). (2017). 2,6,10,15,19,23-hexamethyltetracosane. Retrieved
from https://ccha.curopa.cu/rcgistration-dossicr/-/rcgistcrcd-dossicr/14412
Lyman, Warren J., Reehl, W. F., Rosenblatt, D. H. (1990). Handbook of chemical property estimation
methods: environmental behavior of organic compounds. American Chemical Society
Ruehl, C. R., Nahm T., Isaacman, G., Worton, D. R., Chan, A. W. H., Kolesar, K. R., Cappa, C. D.,
Goldsetin, A. H., Wilson, K. R. (2013) The influence of molecular structure and aerosol phase on the
heterogeneous oxidation of normal and branched alkanes by OH. J. Phys. Chem. A.
Sigma-Aldrich. (2019). Squalane. Retrieved from.
https://www.sigmaaldrich.com/catalog/substance/squalane4228 111 10131 l?lang=en®ion=US
U.S. EPA. (2019). Estimation Programs Interface Suite, v 4.11. United States Environmental
Protection Agency, Washington, DC, USA
4 https://www.epa.gov/sites/prodiKtioii/files/2015-05/documents/05.pdf
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4. Relevant Assessment History
EPA assessed the toxicological profile of squalane and added the chemical to the Safer Choice
Program's Safer Chemical Ingredients List (SCIL) in May 2016 under the functional classes
of emollients and skin conditioning agents. The SCIL5 is a continuously updated list of chemicals that
meet low-concern Safer Choice criteria.6
Internationally, EPA identified one assessment by the Canadian Government, which conducted an
assessment of toxicity and exposure as part of its categorization of the Domestic Substance List and
found that squalane did not meet its criteria for further attention.7
5 https://www.epa.gov/saferchoice/safer-iiigredients
0 https://www.epa.gov/sites/prodiiction/files/2013-12/dociiiiieiits/dfe master criteria safer ingredients v2 l.pdf
7 https://canadacheniicals.oecd.org/CheniicalDeta ils.aspx?ChemicalID=627B506D-7E94-4702-BE15-AlD73E744CFF
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5. Conditions of Use
Per TSCA section 3(4), the term "conditions of use" means the circumstances, as determined by the
Administrator, under which a chemical substance is intended, known, or reasonably foreseen to be
manufactured, processed, distributed in commerce, used, or disposed of. EPA assembled information
on all uses of squalane (Appendix A) to inform which uses would be determined conditions of use.8
One source of information that EPA used to help determine conditions of use is EPA's Chemical Data
Reporting (CDR). The CDR rule (previously known as the Inventory Update Rule, or IUR), under
TSCA section 8, requires manufacturers (including importers) to report information on the chemical
substances they produce domestically or import into the U.S., generally above a reporting threshold of
25,000 lb. per site per year. CDR includes information on the manufacturing, processing, and use of
chemical substances with information dating back to the mid-1980s. CDR may not provide
information on other life-cycle phases such as the chemical substance's end-of-life after use in
products (i.e., disposal).
Based on CDR reporting, squalane is manufactured domestically and imported. It is used in
processing (incorporation into articles, and incorporation into formulations, mixtures, or products) in
toiletries and cosmetics; as well as in lubricants and lubricant additives for consumer and commercial
use (EPA 2017b). According to CDR, squalane is not recycled. No information on disposal is found
in CDR or through EPA's Toxics Release Inventory (TRI) Program9 because squalane is not a TRI-
reportable chemical. Although reasonably available information did not specify additional types of
disposal, for purposes of this proposed prioritization designation, EPA assumed end-of-life pathways
that include releases to air, wastewater, surface water, and land via solid and liquid wastes based on
the conditions of use (e.g., incineration, landfill).
To supplement CDR, EPA conducted research through the publicly available databases listed in
Appendix A (Table A.2) and performed additional internet searches to clarify conditions of use or
identify additional occupational1" and consumer uses. Although EPA identified uses of squalane in
personal care products, this screening review covers TSCA conditions of use for the chemical
substance and personal care products are not considered further in EPA's assessment. Exclusions to
TSCA's regulatory scope regarding "chemical substance" can be found at TSCA section 3(2). Table 3
lists the conditions of use for squalane considered for chemical substance prioritization, per TSCA
section 3(4). Table 3 reflects the TSCA uses determined as conditions of use listed in Table A.3
(Appendix A).
8 Hie prioritization process, including the definition of conditions of use, is explained in the Procedures for Prioritization of
Chemicals for Risk Evaluation Under the Toxic Substances Control Act (82 FR 33753).
9 https://www.epa.gov/toxics-release-inventorv-tri-program
10 Occupational uses include industrial and/or commercial uses
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Table 3: Conditions of Use for Squalane
Life Cycle Stage
Category
Subcategory of Use
Source
Manufacturing
Domestic manufacture
Domestic manufacture
Though not reported to
CDR, manufacturing is
assumed to be reasonably
foreseen.
Import
Import
EPA (2017b)
Processing
Processing- incorporation into
Toiletries/cosmetics - Miscellaneous manufacturing
EPA (2017b)
formulation, mixture or reaction
Lubricants and lubricant additives - All other chemical product and
preparation manufacturing
Distribution
Distribution
Distribution
EPA (2017b)
Not known or reasonably
Fuels and related products
Transformer oil, Vacuum gas oil
NLM (2018), Kirk-Othmer
ascertainable (NKRA)
(2005)
Industrial/commercial/consumer
Paints and coatings
Paints and coatings
ECHA (2018)
uses
Cleaning and furnishing care
products
Cleaning and washing products
ECHA (2018)
Laboratory chemicals
Laboratory chemicals
NLM (2018a); Sigma
Aldrich (2018); ECHA
(2018); SPIN (2018)
Consumer/commercial
Tool sets
CPCat (2019)
Veterinary products
Pet care products
DeLima Associates (2014)
Disposal
Releases to air, wastewater, solid
and liquid wastes
Though not explicitly
identified, releases from
disposal are assumed to be
reasonably foreseen 11
"See Section 5 for a discussion on why releases are assumed to be reasonably foreseen for purposes of this proposed prioritization designation.
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6. Hazard Characterization
EPA reviewed peer-reviewed literature and other data sources to identify reasonably available
information. This literature review approach12 is tailored to capture the reasonably available
information associated with low-hazard chemicals. EPA also used this process to verify the
reasonably available information for reliability, completeness, and consistency. EPA reviewed the
reasonably available information to identify relevant, quality studies to evaluate the hazard potential
for squalane against the endpoints listed below. EPA's New Chemicals Program has used these
endpoints for decades to evaluate chemical substances under TSCA13 and EPA toxicologists rely on
these endpoints as key indicators of potential human health and environmental effects. These
endpoints also align with internationally accepted hazard characterization criteria, such as the
Globally Harmonized System of Classification and Labelling of Chemicals14 as noted above in
Section 4 and form the basis of the comparative hazard assessment of chemicals.
Human health endpoints evaluated: Acute mammalian toxicity, repeated dose toxicity,
carcinogenicity, mutagenicity/genotoxicity, reproductive and developmental toxicity, neurotoxicity,
respiratory and skin sensitization, and eye and skin irritation.
Environmental fate and effects endpoints evaluated: Aquatic toxicity, environmental persistence,
and bioaccumulation and bioconcentration.
The low-concern criteria used to evaluate both human health and environmental fate and effects are
included in Table 4 below.
Table 4: Low-Concern Criteria for Human Health and Environmental Fate and Effects
Human Health
Acute Mammalian
Toxicity15
Very High
High
Moderate
Low
Oral LDso (mg/kg)
<50
>50 - 300
> 300 - 2000
> 2000
Dermal LD50 (mg/kg)
<200
>200- 1000
> 1000- 2000
> 2000
Inhalation LC50
(vapor/gas) (mg/L)
<2
>2-10
>10-20
>20
Inhalation LC50
(dust/mist/fume)
(mg/L)
<0.5
>0.5-1.0
>1.0-5
>5
12Discussed in the document "Approach Document for Screening Hazard Information for Low-Priority Substances Under
TSCA."
13 https://www.epa. gov/sustainable-futures/sustainable-futures-p2-framework-manual
14 https://www.unece.org/fileadmin/DAM/trans/danger/publi/ghs/ghs rev07/English/ST SG AC10 30 Rev7e.pdf
15 Values derived from GHS criteria (Chapter 3.1: Acute Toxicity. 2009, United Nations).
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Table 4: Low-Concern Criteria for Human Health and Environmental Fate and Effects
Repeated Dose
Toxicity (90-day
study)16
High
Moderate
Low
Oral (mg/kg-bw/day)
<10
10-100
> 100
Dermal (mg/kg-
bw/day)
<20
20 - 200
>200
Inhalation
(vapor/gas)
(mg/L/6h/day)
<0.2
0.2-1.0
> 1.0
Inhalation
(dust/mist/fume)
(mg/L/6h/day)
<0.02
0.02-0.2
>0.2
Reproductive
Toxicity17
High
Moderate
Low
Oral (mg/kg/day)
<50
50 - 250
>250
Dermal (mg/kg/day)
<100
100-500
>500
Inhalation (vapor,
gas, mg/L/day)
< 1
1-2.5
>2.5
Inhalation
(dust/mist/fume,
mg/L/day)
<0.1
0.1-0.5
>0.5
Developmental
Toxicity17
High
Moderate
Low
Oral (mg/kg/day)
<50
50 - 250
>250
Dermal (mg/kg/day)
<100
100-500
>500
Inhalation (vapor,
gas, mg/L/day)
< 1
1-2.5
>2.5
Inhalation
(dust/mist/fume,
mg/L/day)
<0.1
0.1-0.5
>0.5
Mutagenicity/
Genotoxicity18
Very High
High
Moderate
Low
Germ cell
mutagenicity
GHS Category 1A
or 1B: Substances
known to induce
heritable mutations
or to be regarded
as if they induce
heritable mutations
in the germ cells of
humans.
GHS Category 2:
Substances which
cause concern for
humans owing to the
possibility that they
may induce heritable
mutations in the germ
cells of humans.
Evidence of
mutagenicity support by
positive results in vitro
OR in vivo somatic cells
of humans or animals
Negative for
chromosomal
aberrations and gene
mutations, or no
structural alerts.
10 Values from GHS criteria for Specific Target Organ Toxicity Repeated Exposure (Chapter 3.9: Specific Target Organ
Toxicity' Repeated Exposure. 2009, United Nations).
17 Values derived from the U.S. EPA's Office of Pollution Prevention & Toxics criteria for HPV chemical categorizations
(Methodology> for Risk-Based Prioritization Under ChM tP), and the EU REACH criteria for Annex IV (2007).
18 From GHS criteria (Chapter 3.5: Germ Cells Mutagenicity. 2009, United Nations) and supplemented with considerations
for mutagenicity and genotoxicity in cells other than germs cells.
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Table 4: Low-Concern Criteria for Human Health and Environmental Fate and Effects
Mutagenicity and
genotoxicity in
somatic Cells
OR
Evidence of
mutagenicity
supported by positive
results in in vitro AND
in vivo somatic cells
and/or germ cells of
humans or animals.
Carcinogenicity19
Very High
High
Moderate
Low
Known or
presumed human
carcinogen (GHS
Category 1A and
1B)
Suspected human
carcinogen (GHS
Category 2)
Limited or marginal
evidence of
carcinogenicity in
animals (and
inadequate20 evidence
in humans)
Negative studies or
robust mechanism-
based structure
activity relationship
(SAR)
Neurotoxicity
(90-day study)16
High
Moderate
Low
Oral (mg/kg-bw/day)
<10
10-100
> 100
Dermal (mg/kg-
bw/day)
<20
20 - 200
>200
Inhalation
(vapor/gas)
(mg/L/6h/day)
<0.2
CD
CM
CD
> 1.0
Inhalation
(dust/mist/fume)
(mg/L/6h/day)
<0.02
0.02-0.2
>0.2
Sensitization21
High
Moderate
Low
Skin sensitization
High frequency of
sensitization in
humans and/or high
potency in animals
(GHS Category 1A)
Low to moderate
frequency of
sensitization in human
and/or low to moderate
potency in animals
(GHS Category 1B)
Adequate data
available and not
GHS Category 1Aor
1B
Respiratory
sensitization
Occurrence in
humans or evidence
of sensitization in
humans based on
animal or other tests
(equivalent to GHS
Category 1A or 1B)
Limited evidence
including the presence
of structural alerts
Adequate data
available indicating
lack of respiratory
sensitization
19 Criteria mirror classification approach used by the IARC (Preamble to the L4RC Monographs: B. Scientific Review and
Evaluation: 6. Evaluation and rationale. 2019J and incorporate GHS classification scheme (Chapter 3.6: Carcinogenicity.
2009, United Nations).
20 EPA's approach to determining the adequacy of information is discussed in the document "Approach Document for
Screening Hazard Information for Low-Priority Substances Under TSCA", also released at proposal.
21 Incorporates GHS criteria {Chapter 3.4: Respiratory or Skin Sensitization. 2009, United Nations).
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Table 4: Low-Concern Criteria for Human Health and Environmental Fate and Effects
Irritation/
Corrosivity22
Very High
High
Moderate
Low
Eye irritation/
corrosivity
Irritation persists
for >21 days or
corrosive
Clearing in 8-21
days, severely
irritating
Clearing in 7 days or
less, moderately
irritating
Clearing in less than
24 hours, mildly
irritating
Skin irritation/
corrosivity
Corrosive
Severe irritation at 72
hours
Moderate irritation at 72
hours
Mild or slight irritation
at 72 hours
Environmental Fate and Effects
Acute Aquatic
Toxicity Value
(L/E/ICso)23
Chronic Aquatic
Toxicity Value
(L/E/ICso)23
Persistence (Measured in terms of level of
biodegradation)24
Bioaccumulation
Potential25
May be low concern
if <10 ppm...
...and <1 ppm...
...and the chemical meets the 10-day window as
measured in a ready biodegradation test...
Low concern if >10
ppm and <100
ppm...
...and >1 ppm and
<10 ppm...
...and the chemical reaches the pass level within
28 days as measured in a ready biodegradation
test
...and BCF/BAF <
1000.
Low concern if >100
ppm...
...and > 10 ppm...
... and the chemical has a half-life < 60 days...
6.1 Human Health Hazard
6.1.1 Absorption, Distribution, Metabolism, Excretion
Absorption
Based on squalanc's low water solubility and molecular weight, squalane is expected to have minimal
absorption from the GI tract following oral exposure.
Following dermal exposure, percutaneous absorption of squalane was described as slight (low
penetration) (CIR Expert Panel. 1982) based on a single study describing the application of
radiolabeled squalane to normal and denuded skin of mice for 60 or 120 minutes (Wepierre et al..
1968).
Based on squalane"s low water solubility, absorption through the lungs is predicted to be low.
22 Criteria derived from the Office of Pesticide Programs Acute Toxicity Categories (U.S. EPA. Label Review Manual.
2010).
23 Derived from GHS criteria (Chapter 4.1: Hazards to the Aquatic Environment. 2009, United Nations), EPA OPPT New
Chemicals Program (Pollution Prevention (P2) Framework, 2005) and OPPT's criteria for HPV chemical categorization
(Methodology> for Risk Based Prioritization Under C1l4MP. 2009).
24 Derived from OPPT's New Chemicals Program and DIE Master Criteria and reflects OPPT policy on PBTs (Design for
the Environment Program Master Criteria for Safer Chemicals, 2010).
25 Derived from OPPT's New Chemicals Program and Arnot & Gobas (2006) [Arnote, J.A. and F.A. Gobas, A review of
bioconcentration factor (BCF) and bioaccimndation factor (B*4F) assessments for organic chemicals in aquatic organisms.
Environmental Reviews, 2006. 14: p. 257-297.]
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Distribution
No quality experimental data26 on squalane's distribution were available. Based on the absorption,
metabolism and excretion information, it is expected that squalane will not be distributed throughout
the body. If ingested, it is expected to be metabolized and excreted (described further below).
Metabolism
Because quality experimental data on squalane metabolite formation were limited, the Quantitative
Structure-Activity Relationship (QSAR) toolbox27 was used to run the in vivo rat metabolism
simulator, the skin metabolism simulator, and the rat liver S9 metabolism simulator. The rat liver S9
metabolism simulator predicted primarily C30 branched primary and tertiary alcohol oxidation
metabolites, the skin metabolism simulator predicted C30 branched primary alcohol oxidation
metabolites, and the in vivo rat metabolism simulator predicted primarily C30 branched tertiary or
primary diols.
Excretion
Minimal excretion data was provided in the preliminary oral study described (Albro and Fishbein.
1970). Four days following oral exposure to squalane, approximately 96% to 100% of the
administered dose was excreted via feces in rats. No detectable amounts of squalane were in the
lymph, bile, or urine samples collected 5, 8, and 72 post exposure. (CIR Expert Panel. 1982; Albro
and Fishbein. 1970). These results indicate following metabolism, squalane will be excreted via feces.
6.1.2 Acute Toxicity
EPA assessed the potential for mammalian toxicity from acute exposures to squalane using the results
of a study following the Method Guideline for Toxicity issued by the Ministry of Health and Welfare
of Japan. Rats exposed by oral gavage to 2000 mg/kg of squalane displayed no mortalities (ECHA.
1995a). A separate oral gavage study in rats exposed to squalane (ECHA. 1996) also reported no
mortalities at the tested dose of 1620 mg/kg. An oral study in mice reported no mortalities at any
dose, including the highest dose of 40,500 mg/kg (CIR Expert Panel. 1982). These studies indicate
low concern for acute toxicity with LD50S greater than the low-concern criteria threshold of 2000
mg/kg.
6.1.3 Repeated Dose Toxicity
EPA assessed the potential for mammalian toxicity from repeated exposures by squalane using a
combined repeated dose, reproductive, and developmental study (ECHA. 2013e). Rats were exposed
to squalane via oral gavage. Males were treated two weeks prior to mating, for a total of 28 days, and
females were treated two weeks prior to mating through postpartum day 4 for a total of 28 days. The
no observed adverse effect level (NOAEL) was 1000 mg/kg-day. This result indicated low concern
for toxicity resulting from repeated exposures by exceeding the oral low-concern threshold of 300
mg/kg-day for a 28-day study (extrapolated from 100 mg/kg-day for a 90-day study).
20 This process is further discussed in the document "Approach Document for Screening Hazard Information for Low-
Priority Substances under TSCA."
27 https://www.oecd.org/chemicalsafetv/risk-assessment/oecd-qsar-toolbox.htm
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6.1.4 Reproductive and Developmental Toxicity
EPA assessed the potential for reproductive and developmental toxicity using the same combined
repeated dose, reproductive, and developmental study discussed above. Rats were exposed to
squalane by oral gavage for 28 days. (ECHA. 2013e). Males were treated two weeks prior to mating
and females were treated two weeks prior to mating through postpartum day 4. No reproductive
(mating, fertility, and estrus cycle) or developmental effects (external examinations of the pups and
pup body weight gain) at the highest dose tested (1000 mg/kg-day) were observed. The NOAEL for
this study was 1000 mg/kg-day for both reproductive and developmental toxicity. These results
indicate low concern for developmental and reproductive toxicity by exceeding the 250 mg/kg-day
threshold.
6.1.5 Genotoxicity
EPA assessed experimental gene mutation and chromosomal aberration studies as an indicator of
squalane"s potential to cause genotoxicity. An in vitro gene mutation study using a mouse lymphoma
cell line exposed to squalane reported negative results with and without activation (ECHA. 2013a).
Studies in two bacteria species, S.typhimiiriiim and E.coli, exposed to squalane both reported negative
results with and without metabolic activation (ECHA. 2011b. 2005). Further, human lymphocytes
exposed to squalane did not cause chromosomal aberrations with and without metabolic activation
(ECHA. 2013b). These negative results in a range of species indicate low concern for squalane to
cause genotoxicity.
6.1.6 Carcinogenicity
Because quality experimental data on squalane were limited, EPA relied on publicly available
quantitative structure activity relationship (QSAR) models and structural alerts (SA) to assess the
carcinogenic potential for squalane, discussed further below.
Structural alerts represent molecular functional groups or substructures that are known to be linked to
the carcinogenic activity of chemicals. The most common structural alerts are those for electrophiles
(either direct acting or following activation). Modulating factors that will impact the carcinogenic
potential of a given electrophile will include its relative hardness or softness, its molecular flexibility
or rigidity, and the balance between its reactivity and stability.28 For squalane and its metabolites,
there is an absence of the types of reactive structural features that are present in genotoxic
carcinogens. Squalane is not an electrophile. ISS profiler, a QSAR model,29 did not identify any
structural alerts for squalane or its metabolites. Further, the Virtual models for property Evaluation of
chemicals within a Global Architecture (VEGA) models"3" results indicate squalane has low potential
to be carcinogenic or mutagenic.
28 "Fundamental and Guiding Principles for (Q)SAR Analysis of Chemical Carcinogens with Mechanistic Considerations:
Series on Testing and Assessment, No. 229." 2015. Environment Directorate, Joint Meeting of the Chemicals Committee
and the Working Party on Chemicals, Pesticides and Biotechnology.
29 Carcinogenicity alerts by ISS 2.4 profiler as encoded in the QSAR Toolbox 4.3 (qsartoolbox.org). A summary of the
results from these models is provided in Appendix B.
30 There are four carcinogenicity models housed within the VEGA 1.1.4 software tool available from
https://www.vegaliub.eu. A summary of the results from these models is provided in Appendix B.
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Squalanc's limited absorption, metabolism, a lack of structural alerts, and experimental genotoxicity
studies indicates that this chemical is unlikely to be carcinogenic or mutagenic.
6.1.7 Neurotoxicity
EPA assessed the potential for neurotoxicity from exposure to squalane on a subset of the exposed
rats from the OECD Guidelines 422 described in Sections 6.1.3 and 6.1.4 used for neurotoxicity
assessments. In the combined repeated dose, reproductive, and developmental study, rats were
exposed to squalane by oral gavage for 28 days and neurotoxicity endpoints were observed in both
adults and pups (ECHA. 2013e). The authors reported that males at 300 and 1000 mg/kg-day
exhibited slightly lower locomotor activity than controls, but these differences were reported to not be
statistically significant. Grip strength, sensory reactivity, and behavior were reported to be equivalent
across all groups. Pups were evaluated for postural reflexes and no effects were observed. Based on
these results, EPA determined the NOAEL to be 1000 mg/kg-day for neurotoxicity. These results
indicate squalane is of low concern of neurotoxicity by exceeding the low-concern threshold of 300
mg/kg-day (extrapolated from 100 mg/kg-day for a 90-day study).
6.1.8 Skin Sensitization
EPA assessed the potential for squalane to act as a skin sensitizing agent using three studies in
humans (ECHA. 2012c. d, 1994b). All of these studies reported negative results for squalane,
indicating low concern for skin sensitization.
6.1.9 Skin Irritation
EPA assessed the potential for squalane to act as a skin irritant using four studies in humans (ECHA.
2012b. c, 1995b. 1994a). which all reported negative results. Two studies in rabbits (ECHA. 2010;
CIR Expert Panel. 1982) also reported negative results for squalane acting as a skin irritant. These
negative results indicate low concern for squalane to cause skin irritation.
6.1.10 Eye Irritation
Quality experimental studies on squalane were limited to assess the potential for squalane to cause
eye irritation. Given the endogenous nature of this chemical and overall low-hazard profile, including
negative results for skin sensitization and skin irritation, EPA anticipates low concern for eye
irritation.
6.1.11 Hazards to Potentially Exposed or Susceptible Subpopulations
The above information supports a low human health hazard finding for squalane based on low-
concern criteria. This finding includes considerations such as the potential for developmental toxicity,
reproductive toxicity, and acute or repeated dose toxicity that may impact potentially exposed or
susceptible subpopulations. Based on the hazard information discussed in Section 6, EPA did not
identify populations with greater susceptibility to squalane.
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6.2 Environmental Hazard
EPA estimated environmental hazard of squalane using experimental data and the Ecological
Structure Active Relationships (ECOSAR) Predictive Model.31 EPA used the quantitative structure
activity relationship (QSAR) for neutral organics. The predicted log K0„ of 8 for squalane exceeds the
acute threshold of log Kow of 5 and chronic threshold of log Kow of 8 for ECOSAR. Thus, ECOSAR
predicts that the physio-chemical properties of squalane, specifically the high octanol water partition
coefficient and low water solubility, limit the dissolved (and bioavailable) concentration of the
chemical in the water column to the extent that environmental toxicity is unlikely to be exhibited.
6.2.1 Acute Aquatic Toxicity
Aquatic vertebrates acutely exposed to squalane for 96 hours reported an LC50 greater than the
highest dose tested, 3.9E-3 mg/L (measured concentration) (ECHA. 2013d). Aquatic invertebrates
exposed to squalane for 48 hours reported no mortality at the highest dose tested, 3.8E-3 mg/L
(measured concentration) (ECHA. 2013c). The effect concentrations for these two trophic levels
exceed the water solubility of squalane, limiting the dissolved (and bioavailable) concentration of the
chemical in the water column to the point that acute toxicity is unlikely to be exhibited. ECOSAR
estimated the same conclusion for algal toxicity based on water solubility and log Kow values for
squalane. These results indicate that squalane is low concern for acute exposures to the aquatic
environment.
6.2.2 Chronic Aquatic Toxicity
ECOSAR estimated the dissolved and bioavailable concentration of the chemical in the water column
required to cause chronic aquatic toxicity could not be reached due to the low water solubility and
high log Kow for squalane. Additionally, biodegradation is expected to further reduce the dissolved
concentration in the environment. These results indicated squalane is low concern for chronic
exposures to the aquatic environment.
6.3 Persistence and Bioaccumulation Potential
6.3.1 Persistence
EPA assessed environmental persistence for squalane using two experimental studies following
OECD Guideline 301 B. One study demonstrated squalane was inherently biodegradable under
aerobic conditions and degraded by more than 67% on day 29 (ECHA. 2011a). The other study
reported squalane as readily biodegradable under aerobic conditions and degraded more than 73% by
day 28 and met the 10-day window (ECHA. 2012a). No degradation products of concern were
identified for this chemical substance, These results indicate low concern for persistence based on the
low-concern threshold of a half-life less than 60 days with no degradation products of concern and
indicate this chemical will have low persistence.
34ittps://www.epa.go v/tsca-screemng-tools/ecological-stmcture-activity-relationships-ecosar-predictive-model
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Anaerobic biodegradation data were not available for squalane. Given the chemical has limited water
solubility and is expected to adsorb to sediments and soil, EPA anticipates low concern for this
chemical in anaerobic environments.
6.3.2 Bioaccumulation Potential
Based on the estimated bioaccumulation factor (BAF) values of 7.7, using the Estimation Programs
Interface (EPI) Suite models,32 squalane has low potential for bioaccumulation in the environment
based on the low-concern threshold of less than 1000.
7. Exposure Characterization
EPA considered reasonably available information on exposure for squalane. In general, there is
limited information on exposure for low-hazard chemicals. EPA identified sources of information
relevant to squalane"s exposure potential, which included the CDR database and other databases and
public sources. Of these sources, the CDR database was the primary source of information on the
conditions of use for this exposure characterization. EPA also consulted sources of use information
from other databases and public sources (listed in Table A.2). EPA used these sources only where
they augmented information from the CDR database to inform intended, known, or reasonably
foreseen uses (Section 5).
As shown in Tables 3 and A.3, squalane is used in processing (incorporation into article, and
incorporation into formulation, mixture, or product) in toiletries and cosmetics and lubricants and
lubricant additives; as well as in paints and coatings and cleaning and furnishing care products for
consumer and commercial use, for example (EPA 2017b). Non-TSCA uses are beyond the scope of
this assessment because of the exclusions under TSCA section 3(2). (See Table A.3).
Under the conditions of use identified in Table 3, EPA assessed the potential exposure to the
following categories: the environment, the general population, and potentially exposed or susceptible
subpopulations including workers and consumers.
7.1 Production Volume Information
Production volume information for squalane is based on an analysis of CDR data reported from 1986
to 2015.33 Prior to 2006, squalane was not reported in the CDR. This does not mean it was not being
produced or imported, but more likely that no single entity site was producing above the reporting
threshold. In reporting year 2006, aggregate production volume for squalane was less than 500,000
lbs. According to CDR, since 2011, production volume has risen from a range of 100,000 lbs to less
than 500,000 lbs. to a range of 1,000,000 lbs. to less than 10,000,000 lbs. in 2014 and 2015.
32 https://www.epa.gov/tsca-screemiig-tools/epi-suitetm-estimation-program-iiiterface
33 Hie CDR requires manufacturers (including importers) to report information on the chemical substances they produce
domestically or import into the U.S. generally above 25,000 lb. per site per year.
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7.2 Exposures to the Environment
EPA expects most exposures to the environment to occur during the manufacturing and processing of
squalane. Exposure is also possible from other uses, such as distribution, consumer, industrial, and
commercial use, and disposal. These activities could result in releases of squalane to media including
surface water, landfills, and air.
Given squalane "s low water solubility, releases to surface water are expected to result in minimal
amounts of squalane present in the water column. The log Koc indicates squalane will adsorb to
sediment and soil particles. Further, EPA expects high levels of removal of squalane during
wastewater treatment (either directly from the facility or indirectly via discharge to a municipal
treatment facility or Publicly Owned Treatment Works (POTW)). Squalane has low persistence
aerobically (discussed in Section 6.3.1) and has the potential to break down in the environment to
carbon dioxide and water. Therefore, any release of the chemical to sediments or soils in aerobic
conditions will break down, reducing exposures to soil-dwelling and benthic organisms.
If disposed of in a landfill, this chemical is expected to degrade under aerobic conditions (discussed in
Section 6.3.1).
If incineration releases during manufacturing and processing occur, EPA expects significant
degradation of squalane to the point that it will not be present in air.
7.3 Exposures to the General Population
EPA expects the general population is unlikely to be exposed to squalane from the potential
environmental releases described above. The general population is unlikely to be exposed through
inhalation of ambient air because it has a low vapor pressure and will break down if incinerated.
Squalane is unlikely to be present in surface water because of its low water solubility (discussed in
Section 3), biodegradability (discussed in Section 6.3.1) and removal through wastewater treatment,
thus reducing the potential for the general population to be exposed by oral ingestion or dermal
exposure. Given the low bioaccumulation or bioconcentration potential of squalane, oral exposure to
squalane via fish ingestion is unlikely.
7.4 Exposures to Potentially Exposed or Susceptible Subpopulations
EPA identified workers as a potentially exposed or susceptible subpopulation based on greater
exposure to squalane than the general population during manufacturing, processing, distribution,
industrial uses, and disposal. EPA also identified consumers as a population that may experience
greater exposure to squalane than the general population through use of cleaning and furnishing care
products, paints and coatings, and pet products, for example.
7.4.1 Exposures to Workers
Based on its reported physical form and measured melting point (Table 2), squalane is a liquid under
ambient conditions. Based on squalane's conditions of use (Table 3), workers may be exposed to
liquids through direct dermal contact with the substance and inhalation of aerosols if they are
generated. Based on its experimental vapor pressure, squalane is not volatile at ambient temperatures,
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minimizing the potential for inhalation of vapors. Dermal exposures are the most likely route of
exposures to workers. If dermal contact occurs, absorption of squalane through skin will be very low.
Workers may be exposed to squalane in manufacturing, processing, distribution, industrial uses and
disposal.
7.4.2 Exposures to Consumers
Consumers could be exposed to squalane through the use of cleaning and furnishing care products,
paints and coatings, and pet care products. For all these uses, if dermal contact does occur, squalane is
expected to be minimally absorbed through the skin. If the chemical is in an aerosol product and
inhalation exposure occurs, absorption of squalane from the lungs is expected to be minimal. EPA
does not include intentional misuse, such as people drinking products containing this chemical, as
part of the known, intended or reasonably foreseen conditions of use that could lead to an exposure
(82 FR 33726). Thus, oral exposures will be incidental (meaning inadvertent and low in volume).
Squalane will be metabolized and excreted, further reducing the duration of exposure.
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8. Summary of Findings
EPA has used reasonably available information on the following statutory and regulatory criteria and
considerations to screen squalane against each of the priority designation considerations in 40 CFR
702.9(a)and discussed individually in this section, under its conditions of use:
the hazard and exposure potential of the chemical substance (See Sections 6 and 7);
persistence and bioaccumulation (See Section 6.3);
potentially exposed or susceptible subpopulations (See Section 7.4);
storage near significant sources of drinking water (See Section 8.4);
conditions of use or significant changes in the conditions of use of the chemical substance
(See Section 5);
the chemical substance's production volume or significant changes in production volume
(See Section 7.1); and
other risk-based criteria that EPA determines to be relevant to the designation of the chemical
substance's priority.
EPA conducted a risk-based, screening-level review based on the criteria and other considerations
above and other relevant information described in 40 CFR 702.9(c) to inform the determination of
whether the substance meets the standard of a high-priority substance. High-priority substance means
a chemical substance that EPA determines, without consideration of costs or other non-risk factors,
may present an unreasonable risk of injury to health or the environment because of a potential hazard
and a potential route of exposure under the conditions of use, including an unreasonable risk to
potentially exposed or susceptible subpopulations identified as relevant by EPA (40 CFR 702.3). This
section explains the basis for the proposed designation and how EPA applied statutory and regulatory
requirements, addressed issues and reached conclusions.
8.1 Hazard and Exposure Potential of the Chemical Substance
Approach: EPA evaluated the hazard and exposure potential of squalane. EPA used this information
to inform its proposed determination of whether squalane would meet the statutory criteria and
considerations for proposed designation as a low-priority substance.
• Hazard potential:
For squalane's hazard potential, EPA gathered information for a broad set of human health and
environmental endpoints described in detail in Section 6 of this document. EPA benchmarked this
information against low-concern thresholds. EPA found that squalane is of low concern for human
health and environmental hazard across the range of endpoints in these low-concern criteria.
• Exposure potential:
To understand exposure potential, EPA gathered information on physical-chemical properties,
production volumes, and the types of exposures likely to be faced by workers, the general population,
and consumers (discussed in Sections 3 and 7). EPA also gathered information on environmental
releases. EPA identified workers, the general population, consumers, and the environment as most
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likely to experience exposures. EPA determined that while the general population, consumers and
workers may be exposed to squalane, exposure by dermal, inhalation and ingestion pathways are
limited by squalane's physical-chemical properties. If squalane is released into the environment, its
exposure potential will be minimal due to low water solubility, and further reduced through
biodegradation.
Rationale: EPA determined that while workers, consumers, and children could be exposed to
squalane during processing, manufacturing, distribution, use, or disposal, these exposures do not pose
a significant risk because of the chemical's low-hazard results across a range of endpoints (discussed
in Section 6). In summary, the concern for exposure is mitigated by the low-hazard profile of this
chemical.
Proposed conclusion: Based on an initial analysis of reasonably available hazard and exposure
information, EPA proposes to conclude that the risk-based screening-level review under 40 CFR
702.9(a)(1) does not support a finding that squalane meets the standard for a high-priority substance.
The reasonably available hazard and exposure information described above provides sufficient
information to support this proposed finding.
8.2 Persistence and Bioaccumulation
Approach: EPA has evaluated both the persistence and bioaccumulation potential of squalane based
on a set of EPA and internationally accepted measurement tools and thresholds that are sound
indicators of persistence and bioaccumulation potential (described in Section 6). These endpoints are
key components in evaluating a chemical's persistence and bioaccumulation potential.
Rationale: EPA review of experimental data indicates squalane is readily biodegradable under
aerobic conditions, with greater than 67 percent biodegradation within 28 days. EPA's EPI Suite
models indicate a low potential for bioaccumulation and bioconcentration.
Proposed conclusion: Based on an initial screen of reasonably available information on persistence
and bioaccumulation, EPA proposes to conclude that the screening-level review under 40 CFR
702.9(a)(2) does not support a finding that squalane meets the standard for a high-priority substance.
The reasonably available persistence and bioaccumulation information described above provides
sufficient information to support this proposed finding.
8.3 Potentially Exposed or Susceptible Subpopulations
Approach: TSCA section 3(12) states that the "term 'potentially exposed or susceptible
subpopulation' means a group of individuals within the general population identified by the
Administrator who, due to either greater susceptibility or greater exposure, may be at greater risk than
the general population of adverse health effects from exposure to a chemical substance or mixture,
such as infants, children, pregnant women, workers, consumers, or the elderly." EPA identified
workers engaged in the manufacturing, processing, distribution, use, and disposal of squalane as a
potentially exposed or susceptible subpopulation (described in more detail in Section 7). Consumers
are also a potentially exposed subpopulation because of their use of cleaning and furnishing care
products, paints and coatings, and pet care products (described in more detail in Section 7).
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Rationale: EPA expects workers and consumers to have a higher exposure to squalane than the
general population. Because of the low-concern hazard profile for squalane, this potential for
exposure does not pose a significant increase in risk for consumers or workers.
Proposed conclusion: Based on the Agency's understanding of the conditions of use and expected
users such as potentially exposed or susceptible subpopulations, EPA proposes to conclude that the
screening-level review under 40 CFR 702.9(a)(3) does not support a finding that squalane meets the
standard for a high-priority substance. While the conditions of use will result in an increase in
exposures to certain populations, the consistently low-concern hazard profile of squalane provides
sufficient evidence to support a finding of low concern. The reasonably available information on
conditions of use, hazard, and exposure described above provides sufficient information to support
this proposed finding.
8.4 Storage Near Significant Sources of Drinking Water
Approach: In Sections 6 and 7, EPA explains its evaluation of the elements of risk relevant to the
storage of squalane near significant sources of drinking water. For this criterion, EPA focused
primarily on the chemical substance's potential human health hazards, including to potentially
exposed or susceptible subpopulations, and environmental fate properties, and explored a scenario of
a release to a drinking water source. EPA also investigated whether the chemical was monitored for
and detected in a range of environmental media. This requirement to consider storage near significant
sources of drinking water is unique to prioritization under TSCA Section 6(b)(1)(A) and 40 CFR
702.9(a)(4).
Rationale: In terms of health hazards, squalane is expected to present low concern to the general
population, including potentially exposed or susceptible subpopulations, across a spectrum of health
endpoints.
In the event of an accidental release into a surface drinking water source, squalane is expected to be
insoluble in water (see Section 3) and has low persistence (see Section 6) in the drinking water
supply. In the event of an accidental release to land, the estimated log Koc indicates this substance is
immobile in soil, which along with its water insolubility, shows a decreased potential to contaminate
groundwater, including well water. Fate and transport evaluations indicate squalane is likely to
partition into sediment, predicted to biodegrade under aerobic conditions, (see Section 3) and unlikely
to bioaccumulate (see Section 6), minimizing the likelihood that the chemical would pose a longer-
term drinking water contamination threat.
A sudden release of large quantities of the chemical near a drinking water source could have
immediate effects on the usability of a surface drinking water source. If such a release were to occur,
two primary factors would operate together to reduce concern. First, the chemical would be expected
to present low concern to the general population, including susceptible subpopulations, across a
spectrum of health endpoints (see Section 6). Second, squalane would likely remain bound to
sediments or soil and degrade in aerobic environments (see Section 6). Together, these factors mean
that any exposures to this chemical through drinking water sources would be short-lived, and that if
ingestion were to take place, concern for adverse health effects would be low. In addition, fate and
transport evaluation indicated squalane would be unlikely to bioaccumulate (see Section 6).
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EPA also explored whether the chemical had been identified as a concern under U.S. environmental
statutes in the past. EPA searched lists of chemicals and confirmed that squalane does not appear on
these lists. The lists reviewed include EPA's List of Lists
(https://www.epa.gov/sites/production/files/2015-03/documents/list of lists.pdf). EPA also searched
the lists of chemicals included in the National Primary Drinking Water Regulations and the
Unregulated Contaminant Monitoring Rule (UCMR) under the Safe Drinking Water Act (SDWA).
Proposed conclusion: Based on a qualitative review of a potential release near a significant source of
drinking water, EPA proposes to conclude that the screening-level review under 40 CFR 702.9(a)(4)
does not support a finding that squalane meets the standard for a high-priority substance. The
reasonably available information on storage near significant sources of drinking water described
above provides sufficient information to support these proposed findings.
8.5 Conditions of Use or Significant Changes in Conditions of Use of the
Chemical Substance
Approach: EPA evaluated the conditions of use for squalane and related potential exposures and
hazards.
Rationale: EPA evaluated the conditions of use of squalane (see Section 5 and Appendix A) and
found it to have a broad range of conditions of use. EPA expects that even if the conditions of use
were to expand beyond activities that are currently known, intended or reasonably foreseen, the
outcome of the screening review would likely not change and would not alter the Agency's
conclusion of low concern. EPA bases this expectation on squalane's consistently low-concern hazard
characteristics across the spectrum of hazard endpoints and regardless of a change in the nature or
extent of its use and resultant increased exposures.
Proposed conclusion: EPA's qualitative evaluation of potential risk does not support a finding that
squalane meets the standard for a high-priority substance, based on its low-hazard profile under the
current conditions of use. EPA proposes to find that even if conditions of use broaden, resulting in an
increase in the frequency or amount of exposures, the analysis conducted to support the screening-
level review under 40 CFR 702.9(a)(5) would not change significantly. In particular, the analysis of
concern for hazard, which forms an important basis for EPA's findings, would not be impacted by a
change in conditions of use. Therefore, such changes would not support a finding that squalane meets
the standard for a high-priority substance. The reasonably available information on conditions of use,
or significant changes in conditions of use, described above provides sufficient information to support
this proposed finding.
8.6 The Volume or Significant Changes in Volume of the Chemical
Substance Manufactured or Processed
Approach: EPA evaluated the current production volumes of squalane (Section 7.1) and related
potential exposures (Sections 7.2 through 7.4).
Rationale: EPA used reasonably available information on production volume (see Appendix A) in
considering potential risk. It is possible that designation of squalane as a low-priority substance could
result in increased use and higher production volumes. EPA expects, however, that any changes in
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squalanc's production volume would not alter the Agency's assessment of low concern given the low-
hazard profile of the chemical. EPA bases this expectation on squalanc's consistently low-concern
hazard characteristics across the spectrum of hazard endpoints. This expectation would apply, even
with a significant change in the volume of the chemical manufactured or processed and resultant
increased exposures.
Proposed conclusion: Based on this screening criteria under 40 CFR 702.9(a)(6), EPA proposes to
find that even if production volumes increase, resulting in an increase in the frequency or levels of
exposures, squalane does not meet the standard for a high-priority substance. The reasonably
available information on production volume, or significant changes in production volume, described
above provides sufficient information to support this proposed finding.
8.7 Other Considerations
EPA did not identify other considerations for the screening review to support the proposed
designation of squalane as a low-priority substance.
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9. Proposed Designation
Based on a risk-based, screening-level review of the chemical substance and, when applicable,
relevant information received from the public and other information as appropriate and consistent
with TSCA section 26(h) and (i), EPA is proposing to designate squalane as a low-priority substance
as it does not meet the statutory criteria for a high-priority substance.
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Appendix A: Conditions of Use Characterization
EPA gathered information on and related to conditions of use including uses of the chemical,
products in which the chemical is used, types of users, and status (e.g., known, regulated).
A.1 CDR Manufacturers and Production Volume
The Chemical Data Reporting (CDR) rule (previously known as the Inventory Update Rule, or IUR),
under TSCA section 8, requires manufacturers (including importers) to report information on the
chemical substances they produce domestically or import into the U.S., generally above a reporting
threshold of 25,000 lb. per site. According to the 2016 Chemical Data Reporting (CDR) database, two
companies manufactured or imported squalane at two sites for reporting year 2015. Individual
production volumes were withheld by EPA to protect against disclosure of CBI.
Table presents the historic production volume of squalane from the CDR from 1986-2015. Prior to
2006, squalane was not reported in the CDR. This does not mean it was not being produced or
imported, but more likely that no single entity site was producing above the reporting threshold. In
reporting year 2006, aggregate production volume for squalane was less than 500,000 lbs. According
to CDR, since 2011, production volume has risen from a range of 100,000 lbs to less than 500,000
lbs.to a range of 1,000,000 lbs. to less than 10,000,000 lbs. in 2014 and 2015.
Table A.1
Pounds)
: 1986-2015 National Production Volume Data for Squalane (Non-Confidential Production Volume in
1986
1990
1994
1998
2002
2006
2011
2012
2013
2014
2015
NDR
NDR
NDR
NDR
NDR
<500 K
A
cn o
o o
100K-
<500 K
500 K-
<1M
1M-
<10M
1M-
<10M
Source(s]
EPA (20.
Note(s):
K = Thous
I:
18a: 2017b: 2006:2002): Sherlock (2019)
sand; M = Million; NDR = No data reported
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A.2 Uses
A.2.1 Methods for Uses Table
Section A. 1 provides a list of known uses of squalane, organized by category of use. To compile the
uses, EPA searched publicly available databases listed in Error! Reference source not found, and
conducted additional Google searches to clarify uses. Search terms differed among databases because
of different search term requirements for each database (i.e., some databases search by CASRN while
others search by chemical name).
Table A.2: Sources Searched for Uses of Squalane
Title Author and Year Search Term(s) Found Use Information?1
Sources searched for all use reports
California Links to
Pesticides Data
California Dept of Pesticide
Regulation (2013)
111-01-3
No
Canada Chemicals
Management Plan
information sheets
Government of Canada
(2018)
Squalane;
Tetracosane
No
Chemical and Product
Categories (CPCat)
Dionisioetal. (2015)
111-01-3
Yes
ChemView2
EPA (2018a)
111-01-3
Yes
Children's Safe Product
Act Reported Data
Washington State Dept. of
Ecology (2018)
111-01-3
No
Consumer Product
Information Database
(CPID)
DeLima Associates (2018)
111-01-3
Yes
Danish surveys on
chemicals in consumer
products
Danish EPA (2018)
N/A, There is no
search, but report titles
were checked for
possible information
on the chemical
Yes
Datamyne
Descartes Datamyne
(2018)
Squalane
No
DrugBank
DrugBank (2018)
111-01-3
No
European Chemicals
Agency (ECHA)
Registration Dossier
ECHA (2018)
111-01-3
Yes
eChemPortal2
OECD (2018)
111-01-3
Yes
Envirofacts2
EPA (2018b)
111-01-3
No
Functional Use Database
(FUse)
EPA (2017a)
111-01-3
Yes
Kirk-Othmer Encyclopedia
of Chemical Technology
Kirk-Othmer (2006)
Squalane
Yes
Non-Confidential 2016
Chemical Data Reporting
(CDR)
EPA (2017b)
111-01-3
Yes
PubChem Compound
Kimetal. (2016)
111-01-3
Yes
Safer Chemical Ingredients
List (SCIL)
EPA (2018d)
111-01-3
Yes
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Table A.2: Sources Searched for Uses of Squalane
Title
Author and Year
Search Term(s)
Found Use Information? 1
Synapse Information
Resources2
Synapse Information
Resources (n.d.)
Squalane;
Tetracosane
No
Resource Conservation
and Recovery Act (RCRA)
EPA (2018c)
Squalane;
Tetracosane
No
Scorecard: The Pollution
Information Site
GoodGuide (2011)
111-01-3
Yes
Skin Deep Cosmetics
Database
EWG (2018)
111-01-3
Yes
Toxics Release Inventory
(TRI)
EPA (2018f)
111-01-3
No
TOXNET2
NLM (2018b)
111-01-3
Yes
Ullmann's Encyclopedia of
Industrial Chemistry
Ullmann's (2000)
Squalane; 111-01-3
No
Additional Sources Identified from Reasonably Available Information
Sigma-Aldrich
Sigma Aldrich (2018)
Incidentally identified
while researching into
details of this
chemical's uses and
products.
Yes
Substances in
Preparations in Nordic
Countries (SPIN)
SPIN (2018)
U.S. EPA InertFinder
EPA (2018e)
U.S. Food and Drug
Administration (FDA)
FDA (2018)
Wedgewood Pharmacy
Wedgewood Pharmacy
(2017)
Note(s):
1. If use information was found in the resource, it will appear in Error! Reference source not found, unless otherwise
noted.
2. This source is a group of databases; thus, the exact resource(s) it led to will be cited instead of the database as whole.
The U.S. Patent and Trademark Office has an online database that shows 6,899 patents referencing
""squalane" (U.S. Patent and Trademark Office (USPTO) 2018). Although patents could be useful in
determining reasonably foreseen uses, it is difficult to confirm whether any of the patented
technologies are currently in use. Uses inferred from patents containing squalane were not included in
Error! Reference source not found.. Note that the uses in Table A.3 that are covered under TSCA
are included in Section 5, Table 3 of this document.
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A.2.2 Uses of Squalane
Table A.3: Uses of Squalane
Use
Expected Users
Description of Use and References
Miscellaneous TSCA Uses
ECHA (2018)
Cleaning and washing products
Consumer, commercial,
industrial
The ECHA registration dossier identifies use of squalane in moist disinfecting wipes in
European countries, including for personal use and paper and board treatment. CPID
identifies two old laundry products, but no current products, that contain squalane. No
further information about this use could be found and it is unknown whether this is an
ongoing use in the United States.
Expected users are based on inclusion in ECHA's consumer uses, uses by
professional workers, and uses at industrial sites.
EPA (2017b); NLM (2018a); Sigma Aldrich (2018); ECHA (2018); SPIN (2018)
Laboratory chemicals
Commercial, industrial
CDR reports use of squalane as a lubricant and lubricant additive in the manufacture of
chemical products and preparations. Haz-Map also identifies use of squalane as a
lubricant. ECHA identifies use as a laboratory reagent, chemical intermediate,
lubricant, grease, release product, pH-regulator, flocculant, precipitant, neutralization
agent, and extraction agent in European countries. SPIN identifies use in the
manufacture of chemicals and chemical products in Nordic countries.
Expected users are industrial based on CDR's Industrial Processing and Use report
and professional based on ECHA's uses by professional workers.
ECHA (2018)
Paints and coatings
Consumer, commercial,
industrial
The ECHA registration dossier identifies use of squalane in consumer and commercial
painting and industrial paints, coatings, paint thinners, and paint removers in European
countries. No further information about this use could be found and it is unknown
whether this is an ongoing use in the United States.
Expected users are based on inclusion in ECHA's consumer uses, uses by
professional workers, and uses at industrial sites.
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Table A.3: Uses of Squalane
Use
Expected Users
Description of Use and References
EPA (2018e); GoodGuide (2011)
Pesticides
Unknown
EPA lists squalane as an inert ingredient approved for nonfood use in the United
States. GoodGuide identifies use of squalane in one miticide. The California
Department of Pesticide Regulation does not list any pesticides currently used in that
state that contain squalane, and the NPIRS does not list any federally active pesticide
products that contain squalane.
Expected users are unknown, due to the limited availability of information.
Pet care
Consumer
DeLima Associates (2014)
CPID generally lists consumer products; therefore, the expected users are consumer.
Dionisioetal. (2015)
Tool sets
Consumer
CPCat identifies use of squalane in tool sets. No further information about this use
could be found and it is unknown whether this is an ongoing use in the United States.
Expected users are consumer based on CPCat's identification under retail product
categories.
NLM (2018a)
Transformer oil
Unknown
Haz-Map identifies use of squalane in transformer oil. No further information about this
use could be found and it is unknown whether this is an ongoing use in the United
States.
Expected users are unknown, due to the limited availability of information.
Kirk-Othmer (2005)
Vacuum gas oil
Unknown
Kirk-Othmer identifies use of squalane in vacuum gas oils. No further information about
this use could be found and it is unknown whether this is an ongoing use in the United
States.
Expected users are unknown, due to the limited availability of information.
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Table A.3: Uses of Squalane
Use
Expected Users
Description of Use and References |
Non-TSCA Uses
EWG (2018); DeLima Associates (2001a)
After shave
Consumer
EWG and CPID identify after shave products that contain squalane, however no
products could be found that are currently for sale and it is unknown whether this is an
ongoing use in the United States.
EWG and CPID generally list consumer products; therefore, the expected users are
consumer.
After sun product
Consumer
EWG (2018)
EWG generally lists consumer products; therefore, the expected users are consumer.
Anti-aging cream
Consumer
EWG (2018)
EWG generally lists consumer products; therefore, the expected users are consumer.
Antiperspirant/ deodorant
Consumer
EWG (2018)
EWG generally lists consumer products; therefore, the expected users are consumer.
EWG (2018); DeLima Associates (2013b)
Around-eye cream
Consumer
EWG and CPID generally list consumer products; therefore, the expected users are
consumer.
Baby lotion
Consumer
EWG (2018)
EWG generally lists consumer products; therefore, the expected users are consumer.
Baby soap
Consumer
EWG (2018)
EWG generally lists consumer products; therefore, the expected users are consumer.
Baby sunscreen
Consumer
EWG (2018)
EWG generally lists consumer products; therefore, the expected users are consumer.
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Table A.3: Uses of Squalane
Use
Expected Users
Description of Use and References
Baby vapor rub
Consumer
EWG (2018)
EWG generally lists consumer products; therefore, the expected users are consumer.
Beauty or blemish (BB) cream
Consumer
EWG (2018)
EWG generally lists consumer products; therefore, the expected users are consumer.
Blush
Consumer
EWG (2018)
EWG generally lists consumer products; therefore, the expected users are consumer.
Body firming lotion
Consumer
EWG (2018)
EWG generally lists consumer products; therefore, the expected users are consumer.
Body oil
Consumer
EWG (2018)
EWG generally lists consumer products; therefore, the expected users are consumer.
Bronzer/highlighter
Consumer
EWG (2018)
EWG generally lists consumer products; therefore, the expected users are consumer.
Color correcting (CC) cream
Consumer
EWG (2018)
EWG generally lists consumer products; therefore, the expected users are consumer.
DeLima Associates (2013a)
Concealer
Consumer
EWG and CPID generally list consumer products; therefore, the expected users are
consumer.
Damaged skin treatment
Consumer
EWG (2018)
EWG generally lists consumer products; therefore, the expected users are consumer.
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Table A.3: Uses of Squalane
Use
Expected Users
Description of Use and References
EWG (2018)
Diaper cream
Consumer
EWG identifies one diaper cream product containing squalane, however this product
does not appear to be for sale, and it is unknown whether this is an ongoing use in the
United States.
EWG generally lists consumer products; therefore, the expected users are consumer.
Eye liner
Consumer
EWG (2018)
EWG generally lists consumer products; therefore, the expected users are consumer.
Eyeshadow
Consumer
EWG (2018)
EWG generally lists consumer products; therefore, the expected users are consumer.
Facial cleanser
Consumer
EWG (2018)
EWG generally lists consumer products; therefore, the expected users are consumer.
Facial moisturizer
Consumer
EWG (2018)
EWG generally lists consumer products; therefore, the expected users are consumer.
Facial powder
Consumer
EWG (2018)
EWG generally lists consumer products; therefore, the expected users are consumer.
Foot moisturizer
Consumer
EWG (2018)
EWG generally lists consumer products; therefore, the expected users are consumer.
Foundation
Consumer
EWG (2018)
EWG generally lists consumer products; therefore, the expected users are consumer.
Hair conditioner
Consumer
EWG (2018)
EWG generally lists consumer products; therefore, the expected users are consumer.
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Table A.3: Uses of Squalane
Use
Expected Users
Description of Use and References
Hair shampoo
Consumer
EWG (2018); DeLima Associates (2001c)
EWG and CPID generally list consumer products; therefore, the expected users are
consumer.
Hair spray
Consumer
EWG (2018)
EWG generally lists consumer products; therefore, the expected users are consumer.
Hair styling aide
Consumer
EWG (2018)
EWG generally lists consumer products; therefore, the expected users are consumer.
Hair treatment/ serum
Consumer
EWG (2018)
EWG generally lists consumer products; therefore, the expected users are consumer.
Hand cream
Consumer
EWG (2018)
EWG generally lists consumer products; therefore, the expected users are consumer.
Lip balm
Consumer
DeLima Associates (2003)
EWG and CPID generally list consumer products; therefore, the expected users are
consumer.
Lip balm with SPF
Consumer
EWG (2018)
EWG generally lists consumer products; therefore, the expected users are consumer.
Lip liner
Consumer
EWG (2018)
EWG generally lists consumer products; therefore, the expected users are consumer.
Lipstick
Consumer
EWG (2018); DeLima Associates (2012)
EWG and CPID generally list consumer products; therefore, the expected users are
consumer.
Makeup primer
Consumer
EWG (2018)
EWG generally lists consumer products; therefore, the expected users are consumer.
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Table A.3: Uses of Squalane
Use
Expected Users
Description of Use and References
Makeup remover
Consumer
EWG (2018)
EWG generally lists consumer products; therefore, the expected users are consumer.
EWG (2018); DeLima Associates (2011)
Makeup with SPF
Consumer
EWG and CPID generally list consumer products; therefore, the expected users are
consumer.
Mascara
Consumer
EWG (2018)
EWG generally lists consumer products; therefore, the expected users are consumer.
Mask
Consumer
EWG (2018)
EWG generally lists consumer products; therefore, the expected users are consumer.
Nail treatment
Consumer
EWG (2018)
EWG generally lists consumer products; therefore, the expected users are consumer.
Oil controller
Consumer
EWG (2018)
EWG generally lists consumer products; therefore, the expected users are consumer.
NLM (2018a); ECHA (2018)
Perfumes
Consumer, commercial, industrial
Haz-Map identifies use of squalane as an additive for perfumes. ECHA identifies use of
squalane in perfumes and fragrances in European countries, however, the
International Fragrance Association (2018) does not include squalane in their list of
standards.
ECHA identifies use in perfumes and fragrances under consumer uses, uses by
professional workers, and uses at industrial sites.
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Table A.3: Uses of Squalane
Use
Expected Users
Description of Use and References
FDA (2018); NLM (2018a); ECHA (2018); Wedgewood Pharmacy (2017)
Pharmaceuticals
Unknown
FDA lists squalane as an approved inactive ingredient in oral powders and topical
augmented creams, emulsion creams, and solutions. Haz-Map identifies use of
squalane as drug additive, and Wedgewood Pharmacy identifies use in non-approved
veterinary drugs. The ECHA registration dossier identifies use of squalane in consumer
pharmaceuticals in European countries. DrugBank does not currently list any drugs
that contain squalane.
Expected users are unknown, due to the limited availability of information.
Serum and essences
Consumer
EWG (2018)
EWG generally lists consumer products; therefore, the expected users are consumer.
Shaving cream
Consumer
EWG (2018)
EWG generally lists consumer products; therefore, the expected users are consumer.
Skin fading/iightener
Consumer
EWG (2018)
EWG generally lists consumer products; therefore, the expected users are consumer.
EWG (2018); Danish EPA (2009); GoodGuide (2011)
Skin moisturizer
Consumer, industrial
EWG and the Danish EPA identify use of squalane in moisturizing creams and lotions.
GoodGuide identifies use of squalane as a softener in cosmetic emollient moisturizers.
EWG generally lists consumer products; therefore, the expected users are consumer.
GoodGuide lists softeners under industrial uses.
EWG (2018); DeLima Associates (2001b)
Skin moisturizer with SPF
Consumer
EWG and CPID generally list consumer products; therefore, the expected users are
consumer.
Styling gel/ lotion
Consumer
EWG (2018)
EWG generally lists consumer products; therefore, the expected users are consumer.
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Table A.3: Uses of Squalane
Use
Expected Users
Description of Use and References
EWG (2018); DeLima Associates (2015)
Sunless tanning
Consumer
EWG and CPID generally list consumer products; therefore, the expected users are
consumer.
Sunscreen
Consumer
EWG (2018)
EWG generally lists consumer products; therefore, the expected users are consumer.
Toners/astringents
Consumer
EWG (2018)
EWG generally lists consumer products; therefore, the expected users are consumer.
Children's Products
CDR reports did not include any uses in children's products; however, uses in baby lotion, soap, sunscreen, and vapor rub are found in this table. Additionally, the Danish
EPA identifies exposure of 2 year-olds to squalane through consumer moisturizing creams and lotions (Danish EPA 2009).
Recycling and Disposal
In the 2016 CDR, both facilities reported not recycling (e.g., not recycled, remanufactured, reprocessed, or reused) squalane (EPA 2017b).
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A.3 References
Amyris Inc. (2014). Squalane Safety Data Sheet. Retrieved from
https://www.lotioncrafter.com/reference/sds neossance squalane.pdf
Brenntag Specialties Inc. (2018). Moisturizing Body Mist. Retrieved from
https://www.brenntag.com/media/documents/bsi/formularies/bsi personal care formulas/moistur
izing body mist 02-152.pdf
California Dept of Pesticide Regulation. (2013). DPR Databases. Retrieved from
https://www.cdpr.ca.gov/dprdatabase .htm
Danish EPA. (2009). Survey and Health Assessment of the exposure of 2 year-olds to chemical
substances in Consumer Products. Retrieved from
https://www2.mst.dk/udgiv/publications/2009/978-87-92548-81-8/pdiy978-87-92548-82-5.pdf
Danish EPA. (2018). Danish surveys on chemicals in consumer products. Retrieved from
https://eng.mst.dk/chemicals/chemicals-in-products/consumers-consumer-products/danish-
survevs-on-consumer-products/
DeLima Associates. (2001a). Nivea for Men After Shave Balm, Mild Cream. Retrieved from
https://www.whatsinproducts.com/tvpes/tvpe detail/l/3461/standard/Nivea%20for%20Men%20
After%20Shave%20Balm.%20Mild%20Cream/14-015-008
DeLima Associates. (2001b). Revlon Moon Drops Soothing Moisture Cream SPF 6. Retrieved from
https://www.whatsinproducts.com/tvpes/tvpe detail/l/4746/standard/Revlon%20Moon%20Drops
%20Soothing%20Moisture%20Cream%20SPF%206/l 8-002-006
DeLima Associates. (2001c). St. Ives Hair Repair Thickening Shampoo Volumizing Treatment For Fine
Hair. Retrieved from
https://www.whatsinproducts.com/tvpes/tvpe detail/l/5674/standard/St.%20Ives%20Hair%20Re
pair%20Thickening%20Shampoo%20Volumizing%20Treatment%20For%20Fine%20Hair/19-
027-001
DeLima Associates. (2003). Avon Beyond Color Nutralush Lip Conditioner. Retrieved from
https://www.whatsinproducts.com/tvpes/tvpe detail/l/170/standard/Avon%20Bevond%20Color
%20Nutralush%20Lip%20Conditioner/01-022-005
DeLima Associates. (2011). Avon Ultra Color Rich Moisture Seduction Lipstick SPF 15. Retrieved
from
https://www.whatsinproducts.com/tvpes/tvpe detail/1/1118 l/standard/Avon%20Ultra%20Color
%20Rich%20Moisture%20Seduction%20Lipstick%20SPF%2015/01 -022-111
DeLima Associates. (2012). Cover Girl Queen Collection Lip Color, All Shades. Retrieved from
https://www.whatsinproducts.com/tvpes/tvpe detail/1/12079/standard/Cover%20Girl%20Queen
%20Collection%20Lip%20Color.%20All%20Shades/16-030-372
DeLima Associates. (2013a). Avon Ideal Flawless Concealer Stick. Retrieved from
https://www.whatsinproducts.com/tvpes/tvpe detail/l/13596/standard/Avon%20Ideal%20Flawle
ss%20Concealer%20Stick/01-022-144
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DeLima Associates. (2013b). Avon Solutions Plus+ Total Radiance Eye Gel. Retrieved from
https://www.whatsinproducts.com/tvpes/tvpe detail/l/13658/standard/Avon%20Solutions%20Pl
us+%20Total%20Radiance%20Eve%20Gel/01 -022-164
DeLima Associates. (2014). Absorbine ShowSheen Showring Shine Original Hair Polish & Detangler.
Retrieved from
https://www.whatsinproducts.com/tvpes/tvpe detail/l/14269/standard/Absorbine%20ShowSheen
%20Showring%20Shine%200riginal%20Hair%20Polish%20&%20Detangler/25-001-006
DeLima Associates. (2015). Olay Total Effects Moisturizer Plus Gradual Sunless Tanner-02/16/2015.
Retrieved from
https://www.whatsinproducts.com/tvpes/tvpe detail/l/17807/standard/p%20class=%22pl%22%3
E01av%20Total%20Effects%20Moisturizer%20Plus%20Gradual%20Sunless%20Tanner-
02/16/2015/p%3E/16-033-164
DeLima Associates. (2018). Consumer Product Information Database. Retrieved from
https ://www.whatsinproducts. com/
Descartes Datamyne. (2018). Descartes Datamyne Import-Export Database.
Dionisio, K. L., Frame, A. M., Goldsmith, M.-R., Wambaugh, J. F., Liddell, A., Cathey, T., . . . Judson,
R. S. (2015). Exploring consumer exposure pathways and patterns of use for chemicals in the
environment. Toxicology! Reports, 2, 228-237. doi:http://dx.doi.org/10.1016/i.toxrep.2014.12.009
DrugBank. (2018). DrugBank Database. Retrieved from https://www.drugbank.ca/
European Chemicals Agency (ECHA). (2018). 2,2-dimethyl-l,3-dioxolan-4-ylmethanol. Retrieved from
https://echa.europa.eu/registration-dossier/-/registered-dossier/12258/3/l/5
EWG. (2018). Squalane. Retrieved from
https://www.ewg.org/skindeep/ingredient/706264/SQUALANE/
GoodGuide. (2011). SQUALANE. Retrieved from http://scorecard.goodguide.com/chemical-
profiles/summarv.tcl?edf substance id=+lll-01-3#use profile
Government of Canada. (2018). Chemical Substances: Services and Information. Retrieved from
https://www.canada.ca/en/health-canada/services/chemical-substances.html
International Fragrance Association (IFRA). (2018). IFRA Standards. Retrieved from
http://www.ifraorg.Org/en-us/standards-librarv#.W-8i5ThKiM8
Kim, S., Thiessen, P. A., Bolton, E. E., Chen, J., Fu, G., Gindulyte, A., . . . Bryant, S. H. (2016).
PubChem Substance and Compound databases. Nucleic Acids Research, -/-/(Database issue),
D 1202-D 1213. doi: 10.1093/nar/gkv951
Kirk-Othmer. (2005). Petroleum.
Kirk-Othmer. (2006). Kirk-Othmer Encyclopedia of Chemical Technology.
Organisation for Economic Cooperation and Development (OECD). (2018). eChemPortal: Global Portal
to Information on Chemical Substances. Retrieved from
https://www.echemportal.org/echemportal/index.action
XIV
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***Proposai Draft - Do Not Cite, Quote or Release During the Review***
Sherlock, Scott (2019). Email to Lynne Blake-Hedges. FW: Teleconference with [Company name CBI]
(Friday-6/21). June 25.
Sigma Aldrich. (2018). Squalane Safety Data Sheet. Retrieved from
https://www.sigmaaldrich.com/MSDS/MSDS/DisplavMSDSPage.do?countrv=US&language=en
&productNumber=234311 &brand=ALDRICH&PageToGoToURL=https%3 A%2F%2Fwww.sig
maaldrich.com%2Fcatalog%2Fproduct%2Faldrich%2F23431 l%3Flang%3Den
Substances in Preparations in Nordic Countries (SPIN). (2018). TETRACOSANE, 2,6,10,15,19,23-
HEXAMETHYL-. Retrieved from http://www.spin2000.net/spinmvphp/?pid=l 11013
Synapse Information Resources, (n.d.). Synapse Information Resources. Retrieved from: Excel file.
U.S. Environmental Protection Agency (EPA). (2002). 1986-2002 Historical IUR Data. Retrieved from
Excel File
U.S. Environmental Protection Agency (EPA). (2006). 2006 IUR Public Database.
U.S. Environmental Protection Agency (EPA). (2017a). Functional Use Database (FUse). Retrieved
from: https://catalog.data.gov/dataset/functional-use-database-fuse
U.S. Environmental Protection Agency (EPA). (2017b). Non-Confidential 2016 Chemical Data Reporting
(CDR). Retrieved from https://www.epa.gov/chemical-data-reporting
U.S. Environmental Protection Agency (EPA). (2018a). ChemView. Retrieved from
https://chemview.epa.gov/chemview
U.S. Environmental Protection Agency (EPA). (2018b). Envirofacts Multisystem Search. Retrieved
from https://www3.epa.gov/enviro/facts/multisvstem.html
U.S. Environmental Protection Agency (EPA). (2018c). Look up table for BR Waste Code (National
Biennial RCRA Hazardous Waste Report). Retrieved from
https://iaspub.epa.gov/enviro/brs codes v2.waste lookup
U.S. Environmental Protection Agency (EPA). (2018d). Safer Chemical Ingredients List. Retrieved from
https://www.epa.gov/saferchoice/safer-ingredients
U.S. Environmental Protection Agency (EPA). (2018e). Squalane. Retrieved from
https://iaspub.epa.gov/apex/pesticides/f?p=INERTFINDER:3:::NO::P3 ID:7417
U.S. Environmental Protection Agency (EPA). (2018f). TRI-Listed Chemicals. Retrieved from
https://www.epa.gov/toxics-release-inventorv-tri-program/tri-listed-chemicals
U.S. Food and Drug Administration (FDA). (2018). squalane. Retrieved from
https://www.accessdata.fda.gov/scripts/cder/iig/index.cfm?event=BasicSearch.page
U.S. National Library of Medicine (NLM). (2018a). Haz-Map®: Information on Hazardous Chemicals
and Occupational Diseases. Retrieved from https://hazmap.nlm.nih.gov/categorv-
details?table=copvtblagents&id=17701
U.S. National Library of Medicine (NLM). (2018b). TOXNET® (TOXicology DataNETwork).
Retrieved from https://toxnet.nlm.nih.gov/cgi-bin/sis/search2
XV
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U.S. Patent and Trademark Office (USPTO). (2018). USPTO Patent Full-Text and Image Database.
Retrieved from http://patft.uspto.gov/nctacgi/nph-
Parser?Sectl=PT02&Sect2=HIT0FF&p=l&u=%2Fnetahtml%2FPT0%2Fsearch-
bool.html&r=0&f=S&l=50&TERMl=saualane&FIELDl=&col=AND&TERM2=&FIELD2=&d
=PTXT
Ullmann's. (2000). ULLMANN'S Encyclopedia of Industrial Chemistry.
Washington State Dept. of Ecology. (2018). Children's Safe Product Act Reported Data. Retrieved from
https://fortress.wa. gov/ecv/cspareporting/
Wedgewood Pharmacy. (2017). LIQUID CHLOR WITH SQUALANE FOR DOGS. Retrieved from
https://www.wedgewoodpetrx.com/learning-center/medication-information-for-pet-and-horse-
owners/liquid-chlor-with-squalene-for-dogs.html
XVI
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Appendix B: Hazard Characterization
Table B.1: Human Health Hazard
ADME
Source
Exposure
Route
Species & strain
(if available)
Duration
Study Details
4968730
Absorption,
Mice
1-2 hours
Methods:
dermal
• Test substance reported as CASRN 111-01-3
• Purity not reported
• GLP not reported
Results:
• 1-hour absorption: 3.05 ± 0.94 ug/cm2, with an average rate of 0.12 nmol/cm2/minute
• 2-hour absorption: 5.25 ± 1.65 ug/cm2, with an average rate 0.103 nmol/cm2/minute
Acute Mammalian Toxicity
Source
Exposure
Route
Species & strain
(if available)
Duration
Doses and replicate
number
Effect
Study Details
5016720
Oral (gavage)
Sprague Dawley
Single dose
Dose: 2000 mg/kg
LDso > 2000 mg/kg
Methods:
rats
followed by 14-
day observation
Replicates: 5 per sex
• Test substance reported as CASRN 111-01-3
• Purity not reported
• Method Guideline for Toxicity Studies issued by
the Ministry of Health and Welfare of Japan
(MHW)
• GLP compliant
5016730
Oral (gavage)
Wistar rats
Single dose
followed by 14-
day observation
Dose: 1620 mg/kg
Replicates: 5 per sex
LD50 > 1620 mg/kg
Methods:
• Test substance reported as CASRN 111-01-3
• Purity not reported
• Method OECD 84/449 L251 (25/04/1984)
• Not GLP compliant
4968730
Oral
Mice
Single dose
Doses: 4050,10125,
20250, and 40500
mg/kg
Replicates: 10-20
per group
LD50 > 40500 mg/kg
Methods:
• Test substance reported as CASRN 111-01-3
• Purity not reported
• GLP compliance not reported
XVII
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Table B.1: Human Health Hazard
Repeated Dose Toxicity
Source
Exposure
Route
Species & strain
(if available)
Duration
Doses and replicate
number
Effect
Study Details
5016708
Oral (gavage)
Wistar Hannover
RccHan;WIST rats
Males were
treated from 2
weeks prior to
mating for a
minimum of 28
days. Females
were treated from
2 weeks prior to
mating through
postpartum day 4
(PD4)
Doses: 0,100, 300,
and 1000 mg/kg
Replicates: 10 per
sex per dose
NOAEL: 1000 mg/kg-
day
Methods:
• Test substance reported as CASRN 111-01-3
• Purity not reported
• OECD Guideline 422
• GLP compliant
Reproductive Toxicity
Source
Exposure
Route
Species & Strain
(if available)
Duration
Doses and replicate
number
Effect
Study Details
5016708
Oral (gavage)
Wistar Hannover
RccHan;WIST rats
Males were
treated from 2
weeks prior to
mating for a
minimum of 28
days. Females
were treated from
2 weeks prior to
mating through
postpartum day 4
(PD4)
Doses: 0,100, 300,
and 1000 mg/kg
Replicates: 10 per
sex per dose
NOAEL: 1000 mg/kg-
day
Methods:
• Test substance reported as CASRN 111-01-3
• Purity not reported
• OECD Guideline 422
• GLP compliant
Developmental Toxicity
Source
Exposure
Route
Species & Strain
(if available)
Duration
Doses and replicate
number
Effect
Study Details
XVIII
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Table B.1: Human Health Hazard
5016708
Oral (gavage)
Wistar Hannover
Males were
Doses: 0,100, 300,
NOAEL: 1000 mg/kg-
Methods:
RccHan;WIST rats
treated from 2
weeks prior to
mating for a
and 1000 mg/kg
Replicates: 10 per
sex per dose
day
• Test substance reported as CASRN 111-01-3
• Purity not reported
• OECD Guideline 422
minimum of 28
days. Females
• GLP compliant
were treated from
2 weeks prior to
mating through
postpartum day 4
(PD4)
Cancer
Source
Effect
Study Details
Oncologic v8.0
Oncologic currently has no assessment criteria regarding diols.
Results:
Structure could not be evaluated by Oncologic.
ISS v2.434
Negative (Estimated)
Methods:
Squalane is a saturated hydrocarbon which does not contain any
structural features indicative of electrophilic potential.
Carcinogenicity alerts (genotoxic and non-genotoxic) by
ISS profiler as available within the OECD Toolbox v4.3
Results:
No alerts were identified for the parent structure or its
metabolites
34 Carcinogenicity alerts by ISS profiler comprises 55 structural alerts for genotoxic and non-genotoxic carcinogenicity. Hie alerts have been compiled upon existing knowledge of
the mechanism of action of carcinogenic chemicals that have been published elsewhere (Benigni andBossa (2011) Chew Rev 111: 2507-2536 andBenigni R et al. (2013) Chew
Rev. 113:2940-2957).
XIX
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Table B.1: Human Health Hazard
VEGA 1.1.435
Squalane was processed through all 4 models. ISS 1.0.2 predicted it to be
Methods:
non-carcinogenic with moderate reliability.
VEGA 1.1.4 contains 4 models for carcinogenicity -
CAESAR 2.1.9, ISS 1.0.2, IRFMN/Antares 1.0.0,
Overall, Squalane is expected not to be carcinogenic based on the VEGA
predictions.
IRFMN/ISSCAN-GX 1.0.0
Results:
• CAESAR 2.1.9: Low reliability (Squalane lies outside
of the applicability domain (AD) of the model)
• ISS 1.0.2: Moderate reliability (Squalane could lie
outside of the AD)
• IRFMN/Antares 1.0.0: Low reliability (Squalane lies
outside of the AD)
• IRFMN/ISSCAN-GX 1.0.0: Low reliability (Squalane
lies outside of the AD)
Genotoxicity
Source
Test Type &
Species & strain
Metabolic
Doses and controls
Results
Study Details
endpoint
(if available)
activation
5016711
Gene mutation
Mouse Lymphoma
With and without
Doses: 65.94-2110 pg/mL
Negative
Methods:
(in vitro)
L5178Y cells
• Test substance reported as CASRN 111-01-3
• Purity not reported
• OECD Guideline 476
• GLP compliant
5016721
Chromosomal
aberrations (in
vitro)
Human
lymphocytes
With and without
Doses: 0.2-5.3 pg/mL
Negative
Methods:
• Test substance reported as CASRN 111-01-3
• Purity: 95%
• OECD Guideline 487
• GLP compliant
35 VEGA 1.1.4 contains 4 different models to facilitate an in silico assessment of carcinogenicity potential. The models are summarized in Golbamaki et al. (2016) J Environ Sci and Health Part C
http://dx.doi.Org/10.1080/10590501.2016.1166879 as well as in documentation that is downloadable from within the VEGA tool itself (https://www.vegahub.eu/).
• CAESAR 2.1.9 is a classification model for carcinogenicity based on a neural network.
• ISS 1.0.2 is a classification model based on the ISS ruleset (as described above for the OECD Toolbox).
• IRFMN/Antares 1.0.0 and IRFMN/ISSCAN-GX1.0.0 are classification models based on a set of rules built with SARpy software (part of the same suite of VEGA tools
https://www.vegahub.eu/) extracted from the Antares and ISSCAN-CGX datasets respectively.
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Table B.1: Human Health Hazard
5016723
Gene mutation
{in vitro)
E. coli
With and without
Doses: 50,100,500,1000 and
5000 |jg/plate
Negative
Methods:
• Test substance reported as CASRN 111-01-3
• Purity not specified
• OECD Guideline 471
• GLP compliant
5016723
Gene mutation
Salmonella
With and without
Doses: 50,100,500,1000 and
Negative
Methods:
(in vitro)
typhimurium
strains TA97a,
TA98, TA100 and
TA1535
5000 |jg/plate
• Test substance reported as CASRN 111-01-3
• Purity not specified
• OECD Guideline 471
• GLP compliant
5016713
Gene mutation
S. typhimurium
With and without
Doses: 50,150,500,1500 and
Negative
Methods
(in vitro)
strains TA1535,
TA1537, TA98,
andTA100
5000 |jg/plate of 50 mg/mL
squalane solution
• Test substance reported as CASRN 111-01-3
• Purity not specified
• OECD Guideline 471
• GLP compliant
5016713
Gene mutation
(in vitro)
E. coli strain WP2
With and without
Doses: 50,150,500,1500 and
5000 |jg/plate of 50 mg/mL
squalane solution
Negative
Methods
• Test substance reported as CASRN 111-01-3
• Purity not specified
• OECD Guideline 471
• GLP compliant
Neurotoxicity
Source
Exposure
Route
Species & Strain
(if available)
Duration
Doses and replicate number
Effect
Study Details
5016708
Oral (gavage)
Wistar Hannover
Males were
Doses: 0,100, 300, and 1000
NOAEL:
Methods:
RccHan;WIST rats
treated from 2
weeks prior to
mating for a
minimum of 28
days. Females
were treated from
2 weeks prior to
mating through
postpartum day 4
(PD4)
mg/kg
Replicates: 10 per sex per dose
1000
mg/kg-day
• Test substance reported as CASRN 111-01-3
• Purity not reported
• OECD Guideline 422
• GLP compliant
Sensitization
XXI
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Table B.1: Human Health Hazard
Source
Exposure
Route
Species & Strain
(if available)
Duration
Doses and replicate number
Effect
Study Details
5016709,
Skin
Humans
24 hours under
Dose: 100% undiluted squalane
Negative
Methods:
5016719
occlusive
conditions 4
times/week for 3
weeks.
Replicates: 110 total, 55 per sex
• Test substance reported as CASRN 111-01-3
• Purity not reported
• Not GLP compliant
5016702
Skin
Humans
24 hours
Dose: 100% undiluted squalane
Replicates: 44 total, 26 females,
18 males
Negative
Methods
• Test substance reported as CASRN 111-01-3
• Purity not reported
• Not GLP compliant
Irritation
Source
Exposure
Route
Species & Strain
(if available)
Duration
Doses
Effect
Study Details
5016715
Skin
Humans
48 hours
Dose: 5% squalane
Replicates: 10 females
Negative
Methods:
• Test substance reported as CASRN 111-01-3.
• Purity not reported
• Not GLP compliant
5016719
Skin
Humans
24 hours under
occlusive
conditions 4
times/week for 3
weeks
Dose: 100% undiluted squalane
Replicates: 110 total, 55 per sex
Negative
Methods:
• Test substance reported as CASRN 111-01-3
• Purity not reported
• Not GLP compliant
5016700
Skin
New Zealand
White rabbits
72 hours
Dose: 0.5 mL undiluted squalane
Replicates: 3 males
Negative
Methods
• Test substance reported as CASRN 111-01-3
• Purity not specified
• Test method: EPA OPPTS 870.2500
• GLP compliant
5016710
Skin
Humans
7 days
Doses: 50,75, and 100% squlane
Replicates: 10 volunteers
Negative
Methods
• Test substance reported as CASRN 111-01-3
• Purity not reported
• Not GLP compliant
4968730
Skin
Rabbits
24 hours
Dose: 0.5 mL undiluted squalane
Negative
Methods
• Test substance reported as CASRN 111-01-3
XXII
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Table B.1: Human Health Hazard
• Purity not reported
• Not GLP compliant
5016703
Dermal Patch
Humans
24-hour
exposure, 48-
hour observation
Dose: unspecified
Replicates: 10 volunteers
Negative
Methods
• Test substance reported as CASRN 111-01-3
• Purity not reported
• Not GLP compliant
XXIII
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Table B.2: Environmental Hazard
Aquatic Toxicity: Experimental
Source
Species &
strain (if
available)
Duration
Doses and replicate
number
Effect
Study Details
5016729
Danio rem
96 hours
Dose: 100 mg/L
(nominal), 3.9 |jg/L
measured
LC50 > 100 mg/L
(nominal)
Methods:
• Test substance reported as CAS RN 111 -01 -3
• Purity not reported
• GLP compliant
Results:
• Substance was concluded to have no effects at saturation (NES)
5016717
Daphnia magna
48 hours
Dose: 100 mg/L
(nominal), 3.9 |jg/L
measured
LCo > 100 mg/L
(nominal)
Methods:
• Test substance reported as CAS RN 111 -01 -3
• Purity not reported
• OECD Guideline 202
• GLP compliant
Results:
• No immobilization observed
• Substance was concluded to have no effects at saturation (NES)
Aquatic Toxicity: Estimated
Model
Species
Predicted Effect
Level
Notes
ECOSAR v2.0
(Class: Neutral
Organics)
Freshwater fish
96-hour LCso: 1.6E-
09 mg/L
NES. LC50 exceeds the estimated water solubility for this substance (3.2E-10 mg/L). Estimated Log K0w
exceeds the endpoint specific cutoff
ECOSAR v2.0
(Class: Neutral
Organics)
Daphnia magna
96-hour EC5o2.9E-
09 mg/L
NES. LC50 exceeds the estimated water solubility for this substance (3.2E-10 mg/L). The estimated log Kow for
this chemical is greater than the endpoint specific cut-off
ECOSAR v2.0
(Class: Neutral
Organics)
Green Algae
96-hour EC50: 2.6E-
07 mg/L
NES.EC50 exceeds the estimated water solubility for this substance (3.2E-10 mg/L). The estimated log K0w for
this chemical is greater than the endpoint specific cut-off
ECOSAR v2.0
(Class: Neutral
Organics)
Green Algae
ChV: 9.3E-07 mg/L
NES. ChV exceeds the estimated water solubility for this substance (3.2E-10 mg/L). The estimated Log K0w for
this chemical is greater than the endpoint specific cut-off
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ECOSAR v2.0
(Class: Neutral
Organics)
Daphnia magna
ChV: 7.2E-09 mg/L
NES. ChV exceeds the estimated water solubility for this substance (3.2E-10 mg/L). The estimated log K0w for
this chemical is greater than the endpoint specific cut-off
ECOSAR v2.0
(Class: Neutral
Organics)
Freshwater fish
ChV: 6.1E-10 mg/L
NES. ChV exceeds the estimated water solubility for this substance (3.2E-10 mg/L). The estimated log K0w for
this chemical is greater than the endpoint specific cut-off
Table B.3: Fate
Environmental Fate: Experimental
Source
Endpoint
Duration
Doses and number of
replicates
Results
Study Details
5016725
Biodegradation,
C02 evolution
28 days
Dose: not specified
• Inherently biodegradable
• 10-day wi ndow was not
met
Methods:
• Test substance reported as CASRN 111-01-3
• Purity not specified
• OECD301B
• GLP compliant
Results:
• 64.7% in 28 days
5016724
Biodegradation,
C02 evolution
28 days
Dose: 27.9 mg/L
Replicates: 3
• Readily biodegradable
• 10-day window met
Methods:
• Test substance reported as CASRN 111-01-3
• Purity not specified
• OECD301B
• Not GLP compliant
Results:
• 77% in 28 days
1525453
Photooxidation
Not
specified
Not specified
Photo-oxidizes with nitrogen
oxides
Methods:
• Test substance reported as CAS RN 111 -01 -3
• Purity not reported
• GLP compliance not reported
• Measured using pure squalane aerosols with average particle
sizes of 103 nm, at 298K (ca. 20°C) and 1 atm, in the absence
of oxygen
Results:
XXV
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• Reactive uptake coefficient for the combined reaction of N2O5
and NO3 when NO3 dominates the oxidation (NO3 + aerosol) =
7.8E-03
• Reactive uptake coefficient for the combined reaction of N2O5
and NO3 when N2O5 dominates the oxidation (N205+aerosol) =
6.2±0.9E-05
2369609
Photooxidation
Not
specified
Not specified
Photo-oxidizes with hydroxyl
radicals
Methods:
• Test substance reported as CAS RN 111 -01 -3
• Purity not reported
• GLP compliance not reported
• Atmospheric pressure flow tube experiment was used to
evaluate hydroxyl-initiated heterogeneous oxidation of pure
squalane aerosols and a-pinene+03 secondary organic coated
squalane aerosols
Results:
• Pure squalane aerosols (average particle size 134 nm):
0 Average reactive uptake coefficient = 0.25±0.05
(0.28±0.06 after diffusion correction)
0 Effective reaction rate coefficient = 1.0E-12 cm3
/molecule-sec
• Coated squalane aerosols (average particle size 169 nm):
0 Average reactive uptake coefficient = 0.45 to 2.9
0 Effective reaction rate coefficient = 3.5-E-12 cm3
/molecule-sec
2464268
Photooxidation
Not
specified
Not specified
Photo-oxidizes with hydroxyl
radicals
Methods:
• Test substance reported as CAS RN 111 -01 -3
• Purity not reported
• GLP compliance not reported
• Flow tube experiment used to evaluate hydroxyl initiated
heterogeneous oxidation of squalane aerosols (mean surface-
weighted diameters of 164 nm)
Results:
• Hydroxyl radical decay rate constant = 1,6±0.4E-12 cm3/
molecule-sec
• Uptake coefficient = 0.36±0.11
• First generation byproduct (by MS): squalane-11-one; both
squalanone and squalanol isomers were isolated as
byproducts
• EPA calculated a half-life of 6.7 days based on this study
XXVI
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2576167
Photooxidation
Not
specified
Not specified
Photo-oxidizes with chlorine
Methods:
• Test substance reported as CAS RN 111 -01 -3
• Purity not reported
• GLP compliance not reported
• Atmospheric photochemical aerosol flow tube experiment
used to evaluate heterogeneous reactions of squalane
particles with gas phase chlorine (CI) radicals in the presence
and absence of oxygen
Results:
• Effective uptake coefficients at < 1 % oxygen
o At [CI2] of 8 ppm = 0.8
o At [CI2] of 32.7 ppm = 3
o At [CI] of 2.67E+09 molecule/cm3 = 2.5
o At [CI] of 2.2E+10 molecule/cm3 = 1.4
• Uptake coefficients were directly related to [CI2] and inversely
related to [CI] due to the competitive rates of chain
propagation and termination
2582128
Photooxidation
Not
specified
Not specified
Photo-oxidizes with hydroxyl
radicals
Methods:
• Test substance reported as CAS RN 111 -01 -3
• Purity not reported
• GLP compliance not reported
• Continuous flow experiment used to evaluate hydroxyl initiated
heterogeneous oxidation of squalane aerosols (average
particle diameter 220±20 nm) at atmospheric pressure and
25°C in the presence of oxygen
Results:
• Reactive uptake coefficient = 0.51 ±0.10 at [OH] = 6.87E+08
• Reactive uptake coefficient = 0.49 to 0.54 at [OH] of 1 to
7E+08 molecule/cm3
• Reaction appears to accelerate at lower concentrations of
hydroxyl radicals
4968700
Photooxidation
Not
specified
Not specified
Photo-oxidizes with hydroxyl
radicals
Methods:
• Test substance reported as CAS RN 111 -01 -3
• Purity not reported
• GLP compliance not reported
• Model system measuring the heterogeneous reaction of OH
radicals with sub-micron squalane particles (average particle
diameter 160 nm) in the presence of oxygen; analysis done
XXVII
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using a photochemical flow reactor combined with AMS
particle analysis
Results:
• Reactive uptake coefficient for squalane was determined to be
0.30±0.07 at an average OH concentration of 1x10E+10
molecules/cm3
• Significant volatilization of the reduced particle would be slow
in the atmosphere; as aerosols become more oxygenated,
volatilization becomes significant for organic material in the
particle phase
Environmental Fate: Modelled
Model
Data Type
Endpoint
Predicted Endpoint
Notes
EPISuite
v.4.11
Estimated
BAF
7.7
EPISuite
v.4.11
Estimated
BCF
3.2 (regression on eq)
EPI Suite
Reference
The measured melting
point and boiling point
were taken from
PhysProp.
EPI Suite (Physical Property Inputs - BP = 350°C, MP = -38°C), SMILES:
CC(C)CCCC(C)CCCC(C)CCCCC(C)CCCC(C)CCCC(C)C
XXVIII
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B.1 References
Albro. PW; Fishbein. L. (1970). Absorption of aliphatic hydrocarbons by rats. Biochim Biophys Acta
219:437-446.
CIR Expert Panel (Cosmetic Ingredient Review Expert Panel). (1982). Final report on the safety
assessment of squalane and squalene. J Am Coll Toxicol 1: 37-56.
Che. PL; Smith. JD; Leone. SR; Ahmed. M; Wilson. KR. (2009). Quantifying the reactive uptake of OH
by organic aerosols in a continuous flow stirred tank reactor. Phys Chem Chem Phys 11: 7885-
7895. http://dx.doi.org/10.1039/b9Q4418c
ECHA (European Chemicals Agency). (1994a). 2,6,10,15,19,23-hexamethyltetracosane: skin
irritation/corrosion: 004 supporting | experimental result, https://ccha.curopa.cu/rcgistration-
dossicr/-/rcgistcrcd-dossicr/14412/7/4/2/'.)documcntUUID= 166fa528-b6d3-4777-bc2a-
b227a84c364d
ECHA (European Chemicals Agency). (1994b). 2,6,10,15,19,23-hexamethyltetracosane: skin
sensitisation: 003 supporting | experimental result, https://echa.europa.eu/registration-dossier/-
/registered-dossier/14412/7/5/2/?documentUUID=4867fc6b-d523-4226-bdf7-c4c700d40a32
ECHA (European Chemicals Agency). (1995a). 2,6,10,15,19,23-hexamethyltetracosane: acute toxicity:
oral: 002 supporting | experimental result. https://echa.europa.eu/registration-dossier/-/registered-
dossier/14412/7/3/2/?documentUUID=8fe3 000d-ce76-43 f4-8f9f-f82b3 6cabcb4
ECHA (European Chemicals Agency). (1995b). 2,6,10,15,19,23-hexamethyltetracosane: skin
irritation/corrosion: 003 supporting | experimental result, https://echa.europa.eu/registration-
dossier/-/registered-dossier/14412/7/4/2/?documentUUID=0e613835-e7a5-4762-b3e4-
eba55002e4f4
ECHA (European Chemicals Agency). (1996). 2,6,10,15,19,23-hexamethyltetracosane: acute toxicity:
oral: 003 supporting | experimental result. https://echa.europa.eu/registration-dossier/-/registered-
dossier/14412/7/3/2/?documentUUID=9d9d89ce-e9d9-4553-9586-b7836cec3178
ECHA (European Chemicals Agency). (2005). 2,6,10,15,19,23-hexamethyltetracosane: genetic toxicity:
in vivo: 001 key | experimental result. https://echa.europa.eu/registration-dossier/-/registered-
dossier/14412/7/7/2
ECHA (European Chemicals Agency). (2010). 2,6,10,15,19,23-hexamethyltetracosane: skin irritation: in
vivo: 001 key | experimental result. https://echa.europa.eu/registration-dossier/-/registered-
dossier/14412/7/4/2
ECHA (European Chemicals Agency). (2011a). 2,6,10,15,19,23-hexamethyltetracosane: biodegradation
in water: screening tests: 001 key | experimental result, https://echa.europa.eu/registration-
dossier/-/registered-dossier/14412/5/3/2
ECHA (European Chemicals Agency). (2011b). 2,6,10,15,19,23-hexamethyltetracosane: genetic toxicity:
in vitro: 002 key | experimental result. https://echa.europa.eu/registration-dossier/-/registered-
dossier/14412/7/7/2/?documentUUID=e4b910bb-72b8-4f60-8cff-8b4e61e6fed7
XXIX
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***Proposal Draft - Do Not Cite, Quote or Release During the Review***
ECHA (European Chemicals Agency). (2011c). 2,6,10,15,19,23-hexamethyltetracosane: biodegradation
in water: screening tests: 001 key | experimental result, https://ccha.curopa.cu/rcgistration-
dossier/-/registered-dossier/14412/5/3/2
ECHA (European Chemicals Agency). (2012a). 2,6,10,15,19,23-hexamethyltetracosane: biodegradation
in water: screening tests: 004 supporting | experimental result, https://ccha.curopa.cu/rcgistration-
dossier/-/registered-dossier/14412/5/3/2/?documentUUID=lflf792c-0997-4f6d-afc3-
f90103cab0ab
ECHA (European Chemicals Agency). (2012b). 2,6,10,15,19,23-hexamethyltetracosane: skin
irritation/corrosion: 005 supporting | experimental result, https://ccha.curopa.cu/rcgistration-
dossier/-/registered-dossier/14412/7/4/2/?documentUUID=f5430888-c730-4e03-84b2-
£5d276045549
ECHA (European Chemicals Agency). (2012c). 2,6,10,15,19,23-hexamethyltetracosane: skin
irritation/corrosion: 006 supporting | experimental result, https://echa.europa.eu/registration-
dossier/-/registered-dossier/14412/7/4/2/?documentUUID=b6e76750-0873-416b-a0e5-
f4d477e95137
ECHA (European Chemicals Agency). (2012d). 2,6,10,15,19,23-hexamethyltetracosane: skin
sensitisation: 004 supporting | experimental result, https://echa.europa.eu/registration-dossier/-
/registered-dossier/14412/7/5/2/?documentUUID=clf6e56c-b3f5-4fc4-8087-10cafd67741b
ECHA (European Chemicals Agency). (2012e). 2,6,10,15,19,23-hexamethyltetracosane: biodegradation
in water: screening tests: 004 supporting | experimental result, https://echa.europa.eu/registration-
dossier/-/registered-dossier/14412/5/3/2/?documentUUID=lflf792c-0997-4f6d-afc3-
f90103cab0ab
ECHA (European Chemicals Agency). (2013a). 2,6,10,15,19,23-hexamethyltetracosane: genetic toxicity:
in vitro: 003 key | experimental result. https://echa.europa.eu/registration-dossier/-/registered-
dossier/14412/7/7/2/?documentUUID=984c0b4e-2081-459e-9172-3780e9028006
ECHA (European Chemicals Agency). (2013b). 2,6,10,15,19,23-hexamethyltetracosane: genetic toxicity:
in vitro: 004. https://echa.europa.eu/registration-dossier/-/registered-
dossier/14412/7/7/2/?documentUUID=737a6cc5-al5a-40fb-8db8-80272a7562ed
ECHA (European Chemicals Agency). (2013c). 2,6,10,15,19,23-hexamethyltetracosane: short-term
toxicity to aquatic invertebrates. https://echa.europa.eu/registration-dossier/-/registered-
dossier/14412/6/2/4
ECHA (European Chemicals Agency). (2013d). 2,6,10,15,19,23-hexamethyltetracosane: short-term
toxicity to fish. https://echa.europa.eu/registration-dossier/-/registered-dossier/14412/6/2/2
ECHA (European Chemicals Agency). (2013e). 2,6,10,15,19,23-hexamethyltetracosane: toxicity to
reproduction. https://echa.europa.eu/registration-dossier/-/registered-dossier/14412/7/9/2
Kolesar. KR; Buffaloe. G; Wilson. KR; Cappa. CD. (2014). OH-initiated heterogeneous oxidation of
internally-mixed squalane and secondary organic aerosol. Environ Sci Technol 48: 3196-3202.
http://dx.doi.org/10.1021/es405177d
Lee. L; Wooldridge. P; Nah. T; Wilson. K; Cohen. R. (2013). Observation of rates and products in the
reaction ofN03 with submicron squalane and squalene aerosol. Phys Chem Chem Phys 15: 882-
892. http://dx.doi.org/10.1039/c2cp42500a
XXX
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Liu. CL; Smith. JD; Che. PL; Ahmed. M; Leone. SR; Wilson. KR. (2011). The direct observation of
secondary radical chain chemistry in the heterogeneous reaction of chlorine atoms with
submicron squalane droplets. Phys Chem Chem Phys 13: 8993-9007.
http ://dx. doi.org/10.103 9/c 1 cp20236g
Ruehl. CR; Nah. T; Isaacman. G; Worton. PR; Chan. AWH; Kolesar. KR; Cappa. CD; Goldstein. AH;
Wilson. KR. (2013). The influence of molecular structure and aerosol phase on the heterogeneous
oxidation of normal and branched alkanes by OH. J Phys Chem A 117: 3990-4000.
http://dx.doi.org/10.1021/ip401888q
Smith. JD; Kroll. JH; Cappa. CD; Che. PL; Liu. CL; Ahmed. M; Leone. S. R.; Worsnop; Wilson. KR.
(2009). The heterogeneous reaction of hydroxyl radicals with sub-micron squalane particles: a
model system for understanding the oxidative aging of ambient aerosols. Atmos Chem Phys
Piscuss 9: 3945-3981. http://dx.doi.org/10.5194/acp-9-3209-2009
Wepierre. J; Cohen. Y; Valette. G. (1968). Percutaneous absorption and removal by the body fluids of
14C ethyl alcohol, 3H perhydrosqualene and 14C p-cymene. Eur J Pharmacol 3: 47-51.
http://dx.doi.org/10.1016/0014-2999(68)90047-2
XXXI
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***Proposal Draft - Do Not Cite, Quote or Release During the Review***
Appendix C: Literature Search Outcomes
C.1 Literature Search and Review
This section briefly describes the literature search and review process, search terms, and search outcomes
for the hazard and fate screening of squalane. Search outcomes and reference details are provided on the
candidate's HERO36 project page.
EPA created a fit-for-purpose process to transparently document the literature search and review37 of
available hazard and fate information for low-priority substance (LPS) candidates. References from peer-
reviewed primary sources, grey sources,58 and other sources were identified, screened at the title/abstract
and full-text level, and evaluated for data quality based on discipline-specific criteria. An overview of the
literature search and review process is illustrated in Figure C1.
Figure C.1: Overview of the Literature Search and Review Process
GO
References available at
title/abstract screening
References available at data quality evaluation
References included in LPS screening reviews
References available at full text screening
References excluded at
full text screening
References excluded at
data quality evaluation
References excluded at
title/abstract screening
References available
from grey literature
and other sources
References available
from primary peer-
reviewed sources
36 The HERO low-priority substance candidate project pages are accessible to the public at littu s: //hero. epa. g o v/hero/.
37 Discussed in the document "Approach Document for Screening Hazard Information for Low-Priority Substances Under
TSCA", also released at proposal.
3^ Grey literature and additional sources are the broad category of studies not found in standard, peer-reviewed literature database
searches. This includes U.S. and international government agency websites, non-government organization (NGO) websites, and
data sources that are difficult to find, or are not included, in the peer-reviewed databases, such as white papers, conference
proceedings, technical reports, reference books, dissertations, and information on various stakeholder websites.
XXXII
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C.1.1 Search Terms and Results
EPA began the literature review process for the hazard screening of squalane by developing search terms.
To gather publicly available information, specific search terms were applied for each discipline and
across databases and grey literature sources. Table C. 1 lists the search terms used in the database search
of peer -reviewed literature for squalane, while Table C.2 lists the search terms used for grey literature
and other secondary sources.
Table C.1: Search Terms Used in Peer-Reviewed Databases
Discipline
Database
Search terms39
Human Health
PubMed
111-01-3[rn] OR"2,6,10,15,19,23-Hexamethyltetracosane"[tw] OR
"Hexamethyltetracosane"[tw] OR "Perhydrosqualene"[tw] OR "Squalan"[tw]
OR"Squalane"[tw] OR "2,6,10,15,19,23-Hexamethyltetra-cosane"[tw] OR
"2,6,10,15,19,23-Hexamethyltetracosan"[tw] OR
"Dodecahydrosqualene"[tw] OR "Hexamethyl tetracosane"[tw] OR
"Phytosqualan"[tw] OR "Phtyosqualan"[tw] OR "Tetracosane,
2,6,10,15,19,23-hexamethyl-"[tw] OR "Cetiol SQ"[tw] OR "Cosbiol"[tw] OR
"Fitoderm"[tw] OR "Mild Finish 20P"[tw] OR "Phytiane LS"[tw] OR "Pripure
3759"[tw] OR "Pripure 379"[tw] OR "Pripure SQV 3759"[tw] OR
"Robane"[tw] OR "Spinacane"[tw] OR "SQ-CONO"[tw] OR "Vitabiosol"[tw]
Toxline
(111-01-3[rn] OR "2,6,10,15,19,23-Hexamethyltetracosane" OR
"Hexamethyltetracosane" OR "Perhydrosqualene" OR "Squalan" OR
"Squalane") AND (ANEUPL [org] OR BIOSIS [org] OR CIS [org] OR DART
[org] OR EMIC [org] OR EPIDEM [org] OR FEDRIP [org] OR HEEP [org]
OR HMTC [org] OR IPA [org] OR RISKLINE [org] OR MTGABS [org] OR
NIOSH [org] OR NTIS [org] OR PESTAB [org] OR PPBIB [org]) AND NOT
PubMed [org] AND NOT pubdart [org]
"2,6,10,15,19,23-Hexamethyltetra-cosane" OR "2,6,10,15,19,23-
Hexamethyltetracosan" OR "Dodecahydrosqualene" OR "Hexamethyl
tetracosane" OR "Phytosqualan" OR "Phtyosqualan" OR "Tetracosane,
2,6,10,15,19,23-hexamethyl-" OR "Cetiol SO" OR "Cosbiol" OR "Fitoderm"
OR "Mild Finish 20P" OR "Phytiane LS" OR "Pripure 3759" OR "Pripure
379" OR "Pripure SQV 3759" OR "Robane" OR "Spinacane" OR "SQ-
CONO" OR "Vitabiosol"
TSCATS1
111-01-3[rn] AND TSCATS[org]
WOS
TS=("111-01-3" OR"2,6,10,15,19,23-Hexamethyltetracosane" OR
"Hexamethyltetracosane" OR "Perhydrosqualene" OR "Squalan" OR
"Squalane" OR"2,6,10,15,19,23-Hexamethyltetra-cosane" OR
"2,6,10,15,19,23-Hexamethyltetracosan" OR "Dodecahydrosqualene" OR
"Hexamethyl tetracosane" OR "Phytosqualan" OR "Phtyosqualan" OR
"Tetracosane, 2,6,10,15,19,23-hexamethyl-" OR "Cetiol SO" OR "Cosbiol"
OR "Fitoderm" OR "Mild Finish 20P" OR "Phytiane LS" OR "Pripure 3759"
OR "Pripure 379" OR "Pripure SQV 3759" OR "Robane" OR "Spinacane"
OR "SQ-CONO" OR "Vitabiosol") AND ((WC=("Toxicology" OR
"Endocrinology & Metabolism" OR "Gastroenterology & Hepatology" OR
"Gastroenterology & Hepatology" OR "Hematology" OR "Neurosciences"
39 Additional language or syntax such as [tw], [rn], [org], and [nm] were added to search terms. These are unique to individual
databases and must be applied to search terms so that the query can run properly.
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Table C.1: Search Terms Used in Peer-Reviewed Databases
OR "Obstetrics & Gynecology" OR "Pharmacology & Pharmacy" OR
"Physiology" OR "Respiratory System" OR "Urology & Nephrology" OR
"Anatomy & Morphology" OR "Andrology" OR "Pathology" OR
"Otorhinolaryngology" OR "Ophthalmology" OR "Pediatrics" OR "Oncology"
OR "Reproductive Biology" OR "Developmental Biology" OR "Biology" OR
"Dermatology" OR "Allergy" OR "Public, Environmental & Occupational
Health") OR SU=("Anatomy & Morphology" OR "Cardiovascular System &
Cardiology" OR "Developmental Biology" OR "Endocrinology & Metabolism"
OR "Gastroenterology & Hepatology" OR "Hematology" OR "Immunology"
OR "Neurosciences & Neurology" OR "Obstetrics & Gynecology" OR
"Oncology" OR "Ophthalmology" OR "Pathology" OR "Pediatrics" OR
"Pharmacology & Pharmacy" OR "Physiology" OR "Public, Environmental &
Occupational Health" OR "Respiratory System" OR "Toxicology" OR
"Urology & Nephrology" OR "Reproductive Biology" OR "Dermatology" OR
"Allergy")) OR (WC="veterinary sciences" AND (TS="rat" OR TS="rats" OR
TS="mouse" OR TS="murine" OR TS="mice" OR TS="guinea" OR
TS="muridae" OR TS=rabbit* OR TS=lagomorph* OR TS=hamster* OR
TS=ferret* OR TS=gerbil* OR TS=rodent* OR TS="dog" OR TS="dogs" OR
TS=beagle* OR TS="canine" OR TS="cats" OR TS="feline" OR TS="pig"
OR TS="pigs" OR TS="swine" OR TS="porcine" OR TS=monkey* OR
TS=macaque* OR TS=baboon* OR TS=marmoset*)) OR (TS=toxic* AND
(TS="rat" OR TS="rats" OR TS="mouse" OR TS="murine" OR TS="mice"
OR TS="guinea" OR TS="muridae" OR TS=rabbit* OR TS=lagomorph* OR
TS=hamster* OR TS=ferret* OR TS=gerbil* OR TS=rodent* OR TS="dog"
OR TS="dogs" OR TS=beagle* OR TS="canine" OR TS="cats" OR
TS="feline" ORTS="pig" ORTS="pigs" ORTS="swine" OR TS="porcine"
OR TS=monkey* OR TS=macaque* OR TS=baboon* OR TS=marmoset*
OR TS="child" OR TS="children" OR TS=adolescen* OR TS=infant* OR
TS="WORKER" ORTS="WORKERS" ORTS="HUMAN" OR TS=patient*
OR TS=mother OR TS=fetal OR TS=fetus OR TS=citizens OR TS=milk OR
TS=formula OR TS=epidemio* OR TS=population* OR TS=exposure* OR
TS=questionnaire OR SO=epidemio*)) OR TI=toxic* OR TS=metaboli* OR
TS=biotransform* OR ((TS="breakdown" OR TS="break-down") AND
(TS=product OR TS=products)))
lndexes=SCI-EXPANDED, CPCI-S, CPCI-SSH, BKCI-S, BKCI-SSH, CCR-
EXPANDED, IC Timespan=AII years
Environmental
Hazard
WOS
TS=("111-01-3" OR"2,6,10,15,19,23-Hexamethyltetracosane" OR
"Hexamethyltetracosane" OR "Perhydrosqualene" OR "Squalan" OR
"Squalane" OR"2,6,10,15,19,23-Hexamethyltetra-cosane" OR
"2,6,10,15,19,23-Hexamethyltetracosan" OR "Dodecahydrosqualene" OR
"Hexamethyl tetracosane" OR "Phytosqualan" OR "Phtyosqualan" OR
"Tetracosane, 2,6,10,15,19,23-hexamethyl-" OR "Cetiol SO" OR "Cosbiol"
OR "Fitoderm" OR "Mild Finish 20P" OR "Phytiane LS" OR "Pripure 3759"
OR "Pripure 379" OR "Pripure SQV 3759" OR "Robane" OR "Spinacane"
OR "SQ-CONO" OR "Vitabiosol") AND ((WC=("Agriculture, Dairy & Animal
Science" OR "Biodiversity Conservation" OR "Biology" OR "Developmental
Biology" OR "Ecology" OR "Entomology" OR "Environmental Sciences" OR
"Environmental Studies" OR "Fisheries" OR "Forestry" OR "Limnology" OR
"Marine & Freshwater Biology" OR "Microbiology" OR "Mycology" OR
"Oceanography" OR "Ornithology" OR "Plant Sciences" OR "Reproductive
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Table C.1: Search Terms Used in Peer-Reviewed Databases
Biology" OR "Zoology")) OR (SU=("Agriculture" OR "Biodiversity &
Conservation" OR "Developmental Biology" OR "Entomology" OR
"Environmental Sciences & Ecology" OR "Fisheries" OR "Forestry" OR
"Marine & Freshwater Biology" OR "Microbiology" OR "Mycology" OR "Plant
Sciences" OR "Reproductive Biology" OR "Zoology" OR "Oceanography"))
OR (TI=toxic*) OR (TS=(ecotox* OR environment* OR phytotox* OR pollut*
OR "A. platyrhynchos" OR "agnatha" OR "agnathan" OR "alligator" OR
"alligators" OR "amphibian" OR "amphibians" OR "amphipod" OR
"amphipoda" OR "amphipods" OR "Anas platyrhynchos" OR "annelid" OR
"annelida" OR "annelids" OR "Antilocapridae" OR "apidae" OR
"Aplodontidae" OR "Apoidea" OR "aquatic" OR "archiannelid" OR
"archiannelida" OR "Arvicolinae" OR "aves" OR "avian" OR "avians" OR
"badger" OR "badgers" OR "barnacle" OR "barnacles" OR "bass" OR "bear"
OR "bears" OR "beaver" OR "beavers" OR "bee" OR "bees" OR "bird" OR
"birds" OR "bivalve" OR "bivalves" OR "bleak" OR "bluegill" OR "bluegills"
OR "bluehead" OR "bobwhite" OR "bobwhites" OR "Bovidae" OR "C. carpio"
OR "caiman" OR "Canidae" OR "carp" OR "Castoridae" OR "catfish" OR
"cephalopod" OR "cephalopoda" OR "cephalopods" OR "Cervidae" OR
"chicken" OR "chickens" OR "chiselmouth" OR "clam" OR "clams" OR
"cockle" OR "cockles" OR "cod" OR "copepod" OR "copepoda" OR
"copepods" OR "coturnix" OR "crab" OR "crabs" OR "crappie" OR
"crappies" OR "crayfish" OR "croaker" OR "crocodile" OR "crocodiles" OR
"crustacea" OR "crustacean" OR "crustaceans" OR "Cyprinus carpio" OR
"D. magna" OR "D. rerio" OR "dace" OR "Danio rerio" OR "daphnia" OR
"Daphnia magna" OR "darter" OR "darters" OR "Dasypodidae" OR
"Dicotylidae" OR "Didelphidae" OR "Dipodidae" OR "dog" OR "dogs" OR
"dogfish" OR "duck" OR "duckling" OR "ducklings" OR "ducks" OR
"earthworm" OR "earthworms" OR "ec50" OR "ec50s" OR "echinoderm" OR
"echinoderms" OR "eel" OR "eels" OR "elasmobranch" OR "Equidae" OR
"Erethizontidae" OR "Felidae" OR "ferret" OR "fish" OR "fisher" OR "fishers"
OR "fishes" OR "flagfish" OR "flatworm" OR "flatworms" OR "flounder" OR
"frog" OR "frogs" OR "galaxias" OR "gallus" OR "gastropod" OR
"gastropoda" OR "gastropods" OR "Geomyidae" OR "goldfish" OR
"gourami" OR "gouramy" OR "Green Algae" OR "grunion" OR "guppies" OR
"guppy" OR "haddock" OR "hagfish" OR "haplodrili" OR "Harvest mice" OR
"Harvest mouse" OR "herring" OR "Heteromyidae" OR "honeybee" OR
"honeybees" OR "hooknose" OR "inanga" OR "killifish" OR "L. idus" OR "L.
macrochirus" OR "lamprey" OR "lampreys" OR "Ic50" OR "Ic50s" OR "leech"
OR "lemming" OR "Lepomis macrochirus" OR "Leporidae" OR "lethal
concentration" OR "Leuciscus idus" OR "lizard" OR "lizards" OR "lobster"
OR "lobsters" OR "macroinvertebrate" OR "macroinvertebrates" OR
"mallard" OR "mallards" OR "marten" OR "medaka" OR "menhaden" OR
"Microtus" OR "milkfish" OR "mink" OR "minnow" OR "minnows" OR
"mollusc" OR "molluscs" OR "mollusk" OR "mollusks" OR "molly" OR
"mrigal" OR "mudfish" OR "mudsucker" OR "mulles" OR "mullet" OR
"mummichog" OR "mummichogs" OR "mussel" OR "mussels" OR
"Mustelidae" OR "Myocastoridae" OR "Mysid shrimp" OR "newt" OR "newts"
OR "northern pike" OR "0. latipes" OR "0. mykiss" OR "Ochotonidae" OR
"octopi" OR "octopus" OR "oligochaeta" OR "oligochaete" OR
"Oncorhynchus mykiss" OR "Onychomys" OR "opossum" OR "Oryzias
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Table C.1: Search Terms Used in Peer-Reviewed Databases
latipes" OR "oyster" OR "oysters" OR "P. promelas" OR "P. reticulata" OR
"P. subcapitata" OR "perch" OR "Peromyscus" OR "Pimephales promelas"
OR "pinfish" OR "pinfishes" OR "planaria" OR "planarian" OR "Poecilia
reticulata" OR "polychaeta" OR "polychaete" OR "polychaetes" OR
"Procyonidae" OR "Pseudokirchneriella subcapitata" OR "puffer" OR
"puffers" OR "pumpkinseed" OR "pumpkinseeds" OR "pupfish" OR "quahog"
OR "quahogs" OR "quail" OR "quails" OR "rasbora" OR "rasboras" OR
"Reithrodontomys" OR "reptile" OR "reptiles" OR "rohu" OR "S.
erythrophthalmus" OR "S. quadricauda" OR "S. subspicatus" OR
"salamander" OR "salamanders" OR "salmon" OR "scallop" OR "scallops"
OR "Scardinius erythrophthalmus" OR "Scenedesmus quadricauda" OR
"Scenedesmus subspicatus" OR "Sciuridae" OR "sea anemone" OR "sea
anemones" OR "sea cucumber" OR "sea cucumbers" OR "sea urchin" OR
"sea urchins" OR "seabass" OR "seabream" OR "shark" OR "sharks" OR
"shiner" OR "shiners" OR "shrimp" OR "Sigmodon" OR "Sigmodontinae" OR
"silverside" OR "silversides" OR "skunk" OR "skunks" OR "snake" OR
"snakehead" OR "snakes" OR "songbird" OR "songbirds" OR "Soricidae"
OR "squid" OR "starfish" OR "stickleback" OR "sticklebacks" OR "sting ray"
OR "sting rays" OR "sucker" OR "suckers" OR "Suidae" OR "sunfish" OR
"Talpidae" OR "teleost" OR "teleostei" OR "teleosts" OR "terrapin" OR
"terrapins" OR "tilapia" OR "tilapiaz" OR "toad" OR "toadfish" OR
"toadfishes" OR "toads" OR "tortoise" OR "tortoises" OR "trout" OR
"tubificid" OR "tubificidae" OR "tubificids" OR "turkey" OR "turkeys" OR
"turtle" OR "turtles" OR "Ursidae" OR "vole" OR "walleye" OR "walleyes" OR
"water flea" OR "water fleas" OR "waterbird" OR "waterbirds" OR
"waterfowl" OR "waterfowls" OR "weakfish" OR "weasel" OR "whelk" OR
"whelks" OR "wildlife")))
lndexes=SCI-EXPANDED, CPCI-S, CPCI-SSH, BKCI-S, BKCI-SSH, CCR-
EXPANDED, IC Timespan=AII years
Toxline Same as human health strategy synonyms only
TSCATS 1 Same as human health strategy CASRN only
Proquest TITLE=("111-01-3" OR "2,6,10,15,19,23-Hexamethyltetracosane" OR
"Hexamethyltetracosane" OR "Perhydrosqualene" OR "Squalan" OR
"Squalane" OR "Dodecahydrosqualene" OR "Hexamethyl tetracosane" OR
"Tetracosane, 2,6,10,15,19,23-hexamethyl-" OR "Mild Finish 20P") OR
ABSTRACT=("111-01-3" OR "2,6,10,15,19,23-Hexamethyltetracosane" OR
"Hexamethyltetracosane" OR "Perhydrosqualene" OR "Squalan" OR
"Squalane" OR "Dodecahydrosqualene" OR "Hexamethyl tetracosane" OR
"Tetracosane, 2,6,10,15,19,23-hexamethyl-" OR "Mild Finish 20P") OR
SUBJECT=("111-01-3" OR "2,6,10,15,19,23-Hexamethyltetracosane" OR
"Hexamethyltetracosane" OR "Perhydrosqualene" OR "Squalan" OR
"Squalane" OR "Dodecahydrosqualene" OR "Hexamethyl tetracosane" OR
"Tetracosane, 2,6,10,15,19,23-hexamethyl-" OR "Mild Finish 20P")
"2,6,10,15,19,23-Hexamethyltetra-cosane" OR "2,6,10,15,19,23-
Hexamethyltetracosan" OR "Phytosqualan" OR "Phtyosqualan" OR "Cetiol
SO" OR "Cosbiol" OR "Fitoderm" OR "Phytiane LS" OR "Pripure 3759" OR
"Pripure 379" OR "Pripure SQV 3759" OR "Robane" OR "Spinacane" OR
"SQ-CONO" OR "Vitabiosol"
XXXVI
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***Proposal Draft - Do Not Cite, Quote or Release During the Review***
Table C.1: Search Terms Used in Peer-Reviewed Databases
Fate
WOS
TS=("111-01-3" OR"2,6,10,15,19,23-Hexamethyltetracosane" OR
"Hexamethyltetracosane" OR "Perhydrosqualene" OR "Squalan" OR
"Squalane" OR"2,6,10,15,19,23-Hexamethyltetra-cosane" OR
"2,6,10,15,19,23-Hexamethyltetracosan" OR "Dodecahydrosqualene" OR
"Hexamethyl tetracosane" OR "Phytosqualan" OR "Phtyosqualan" OR
"Tetracosane, 2,6,10,15,19,23-hexamethyl-" OR "Cetiol SO" OR "Cosbiol"
OR "Fitoderm" OR "Mild Finish 20P" OR "Phytiane LS" OR "Pripure 3759"
OR "Pripure 379" OR "Pripure SQV 3759" OR "Robane" OR "Spinacane"
OR "SQ-CONO" OR "Vitabiosol") AND TS=(adsorp* OR aerob* OR
anaerob* OR bioaccumuiat* OR bioavaii* OR bioconcentrat* OR biodegrad*
OR biomoni* OR biotrans* OR degrad* OR dispers* OR fish* OR hydroly*
leach* OR migrat* OR partic* OR partition* OR persisten* OR photoly* OR
volatil* OR abiotic OR absorb OR absorption OR accumulation-rate OR
aerosol OR aerosols OR air OR anoxic OR atm-m3/mol OR
biomagnification OR biosolids OR biota OR breakdown-product OR
breakdown-products OR chelation OR coagulation complexation OR decay-
rate OR diffusion-coefficient OR dissolution OR dust OR effluent OR
environmental-fate OR evaporation-from-water OR excretion OR
flocculation OR flux OR fugacity OR gas-phase-mass-transfer OR ground-
water OR groundwater OR half-life OR henry1 s-law OR incinerate OR
incineration OR indoor-outdoor-ratio OR influent OR ingestion OR intake OR
kinetics OR liquid-phase-mass-transfer OR mass-transfer-coefficient OR
microcosm OR modified-state-space OR particle-size OR particulate OR
pathway OR pathways OR penetration-factor OR penetration-ratio OR
photostability OR placenta OR plasma OR plume OR point-source OR
point-sources OR pore-water OR pretreatment-program OR redox OR
sediment OR serum OR sewage-treatment OR sludge OR soil OR
subsurface-intrusion OR surface-water-concentration OR time-weighted-
average OR transfer OR transformation OR trophic-magnification OR vapor
OR wait-time OR wastewater-treatment OR weight-fraction OR wildlife OR
BAF OR BCF OR BSAF OR BSAFs OR KAW OR Kd OR KOA OR KOC OR
POTW OR SES OR WWTP OR ((OECD OR OPPTS OR OCSPP) AND
(Guideline OR guidelines)))
lndexes=SCI-EXPANDED, CPCI-S, CPCI-SSH, BKCI-S, BKCI-SSH, CCR-
EXPANDED, IC Timespan=AII years
Table C.2: Search Terms Used in Grey Literature and Additional Sources
Chemical
Search terms
Squalane
Searched as a string or individually depending on resource: "111-01-3" OR "2,6,10,15,19,23-
Hexamethyltetracosane" OR "Hexamethyltetracosane" OR "Perhydrosqualene" OR "Squalan" OR "Squalane"
OR "2,6,10,15,19,23-Hexamethyltetra-cosane" OR "Dodecahydrosqualene" OR "Hexamethyl tetracosane" OR
"Tetracosane, 2,6,10,15,19,23-hexamethyl-"
After the search terms were applied, more than 750 references were returned by all search efforts across
peer-reviewed databases and grey literature sources. The total number of references include database
results and additional strategies. All references from the search efforts were screened and evaluated
through the LPS literature search and review process.37 Of these, 29 references were included for data
XXXVII
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evaluation and used to support the designation of squalane as LPS. The included hazard and fate
references are listed in the bibliography of Appendix B.
C.2 Excluded Studies and Rationale
This section lists the excluded references, by HERO ID, found to be off-topic or unacceptable for use in
the hazard screening of squalane. The excluded references are organized by discipline (human health
hazard, environmental hazard, and fate), presented along with a rationale based on exclusion criteria. The
criteria37 was used to determine off-topic references in the title/abstract or full-text screening and to
determine unacceptable references in the data quality evaluation are provided in the form of questions.
C.2.1 Human Health Hazard Excluded References
For the screening review of squalane, EPA excluded a total of 173 references when assessing human
health hazard. Off-topic references (e.g., studies that did not contain information relevant to human
health) were excluded at either title/abstract screening (see Table C.3), or full-text screening (see Table
C.4). Unacceptable references (e.g., studies that did not meet data quality metrics) were excluded at full-
text screening (see Table C.5). Off-topic and unacceptable references are displayed next to the
corresponding exclusion criteria.
XXXVIII
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Table C.3: Off-Topic References Excluded at Title/Abstract Screening for Human Health Hazard
Reference excluded (HERO ID) because the reference did NOT contain information needs40 relevant to human health hazard
4968686
4220587
4968694
4968817
4968965
4969085
4969209
4969269
4969193
4969258
900143
4220639
4968695
4968818
4968974
4969087
4969213
4969302
4969194
4969259
1085060
4220663
4968696
4968819
4968975
4969089
4969214
4969308
4969196
4969260
1169594
4271866
4968697
4968822
4968976
4969092
4969243
4969318
4969203
4969261
1525453
4293599
4968725
4968877
4968977
4969093
4969244
4969323
4969205
4969265
2337930
4332124
4968728
4968882
4968980
4969094
4969245
4969325
4969206
4969266
2463015
4354932
4968733
4968888
4968984
4969098
4969246
4969326
4969207
4969268
2464268
4654666
4968734
4968889
4969014
4969100
4969248
4969334
4968896
4968811
2551928
4864460
4968735
4968890
4969015
4969188
4969250
4969022
4968897
4968812
2568604
4886462
4968802
4968891
4969016
4969189
4969253
4969059
4968917
4968813
2576167
4947185
4968804
4968892
4969017
4969191
4969255
4969071
4968918
4968814
2582128
4968663
4968805
4968893
4969018
4968691
3603188
4969073
4968922
4968816
3005691
4968682
4968806
4968894
4969020
4968693
3813615
4969075
3014628
4968685
3005703
4968683
3014637
Reference excluded (HERO ID) because the reference primarily contained in silico data
N/A
Table C.4: Screening Questions and Off-Topic References Excluded at Full-Text Screening for Human Health Hazard
Question
Off-topic if answer is:
References excluded (HERO ID)
Does the reference contain information pertaining
to a low- priority substance candidate?
No
76242
1618382
2052970
40 Hie information needs for human health hazard includes a list of study characteristics pertaining to the study population/test organism, types of exposures and routes, use of
controls, type and level of effects. A complete list of the information needs is provided in Table A1 of the "Approach Document for Screening Hazard Information for Low-
Priority Substances Under TSCA". These information needs helped guide the development of questions for title/abstract and full-text screening.
XXXIX
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Table C.4: Screening Questions and Off-Topic References Excluded at Full-Text Screening for Human Health Hazard
4968657
4968658
4968766
4968809
4968878
4969078
What type of source is this reference?
Review article or book chapter that contains only
citations to primary literature sources
4968716
What kind of evidence does this reference
primarily contain?
In silico studies that DO NOT contain experimental
verification
N/A
The following question apply to HUMAN evidence only
Does the reference report an exposure route that
is or is presumed to be by an inhalation, oral, or
dermal route?
No
N/A
Does the reference report both test substance
exposure(s) AND related health outcome(s)?
No
N/A
If the reference reports an exposure to a chemical
mixture, are measures of the test substance or
related metabolite(s) reported independently of
other chemicals?
Note: If the paper does not pertain to mixtures,
choose "Not Applicable".
No
N/A
The following question apply to ANIMAL evidence only
Does the reference report an exposure route that
is by inhalation, oral, or dermal route?
No
N/A
Does the reference report both test substance-
related exposure(s) AND related health
outcome(s)?
No
N/A
Does the reference report the duration of
exposure?
No
4968724
Does the reference report an exposure to the test
substance only (i.e. no mixtures with the exception
No
63197
4969080
1407194
XL
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***Proposal Draft - Do Not Cite, Quote or Release During the Review***
Table C.4: Screening Questions and Off-Topic References Excluded at Full-Text Screening for Human Health Hazard
of aqueous solutions and reasonable impurities
and byproducts)?
Does the paper report a negative control that is a
vehicle control or no treatment control?
No41
4968724
The following questions apply to MECHANISTIC/ALTERNATIVE TEST METHODS evidence only
Does the reference report a negative control that is
a vehicle control or no treatment control?
No
N/A
Does the reference report an exposure to the test
substance only (i.e. no mixtures with the exception
of aqueous solutions and reasonable impurities
and byproducts)?
No
N/A
For genotoxicity studies only: Does the study use a
positive control?
No
N/A
Table C.5: Data Quality Metrics and Unacceptable References Excluded at Data Quality Evaluation for Human Health Hazard - Animal
Data Quality Metric
Unacceptable if:
References excluded (HERO ID)
Metric 1:
Test substance identity
• The test substance identity cannot be
determined from the information provided
(e.g., nomenclature was unclear and
CASRN or structure were not reported).
OR
• For mixtures, the components and ratios were
not characterized or did not include information that
could result in a reasonable approximation of
components.
N/A
Metric 2:
Negative and vehicle controls
A concurrent negative control group was not
included or reported.
OR
The reported negative control group was not
appropriate (e.g., age/weight of animals differed
between control and treated groups).
N/A
41 Except for acute mammalian toxicity and skin and eye irritation studies, where the me of a negative control may not be required (e.g., OECD 403 Acute Inhalation Toxicity
Guidelines).
XLI
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***Proposal Draft - Do Not Cite, Quote or Release During the Review***
Table C.5: Data Quality Metrics and Unacceptable References Excluded at Data Quality Evaluation for Human Health Hazard - Animal
Data Quality Metric
Unacceptable if:
References excluded (HERO ID)
Metric 3:
When applicable, an appropriate concurrent positive
N/A
Positive controls
control (i.e., inducing a positive response) was not
used.
Metric 4:
Doses/concentrations were not reported and could
5016704
Reporting of doses/concentrations
not be calculated using default or reported
5016714
estimates of body weight and diet/water intake (e.g.,
5016716
default intake values are not available for pregnant
1619553
animals).
4968670
4968730
5016698
5016699
5016705
5016706
Metric 5:
The duration of exposure was not reported.
5016704
Exposure duration
OR
5016714
The reported exposure duration was not suited to
4968730
the study type and/or outcome(s) of interest (e.g.,
5016712
<28 days for repeat dose).
Metric 6:
The test animal species was not reported.
1619655
Test animal characteristics
OR
4829875
The test animal (species, strain, sex, life-stage,
4968670
source) was not appropriate for the evaluation of
4968730
the specific outcome(s) of interest (e.g., genetically
modified animals, strain was uniquely susceptible or
resistant to one or more outcome of interest).
Metric 7:
The number of animals per study group was not
N/A
Number of animals per group
reported.
OR
The number of animals per study group was
insufficient to characterize toxicological effects (e.g.,
1-2 animals in each group).
XLII
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***Proposal Draft - Do Not Cite, Quote or Release During the Review***
Table C.5: Data Quality Metrics and Unacceptable References Excluded at Data Quality Evaluation for Human Health Hazard - Animal
Data Quality Metric
Unacceptable if:
References excluded (HERO ID)
Metric 8:
Outcome assessment methodology
The outcome assessment methodology was not
sensitive for the outcome(s) of interest (e.g.,
evaluation of endpoints outside the critical window
of development, a systemic toxicity study that
evaluated only grossly observable endpoints, such
as clinical signs and mortality, etc.).
5016704
5016714
1619553
3044744
5016712
Metric 9:
Reporting of data
Data presentation was inadequate (e.g., the
report does not differentiate among findings in
multiple exposure groups).
OR
Major inconsistencies were present in reporting of
results.
5016714
4968730
C.2.2 Environmental Hazard
For the screening review of LPS candidate squalane, EPA excluded a total of 271 references when assessing environmental hazard. Off-topic
environmental hazard references excluded at title/abstract screening are listed in Table C.6, and those excluded at full-text screening are listed in
Table C.7. References in Table C.8 represent unacceptable studies based on specific data quality metrics for environmental hazard. Off-topic and
unacceptable references are displayed next to the corresponding exclusion criteria.
Table C.6: Off-Topic References Excluded at Title/Abstract Screening for Environmental Hazard
Reference excluded (HERO ID) because the reference did NOT contain information needs42 relevant to environmental hazard
4968714
4829875
4968715
4968823
4968863
4968905
2477014
4968992
4968768
1619655
4968898
4968645
4968716
4968824
4968865
4968906
2521944
4968997
4968769
1621432
4968899
4968646
4968717
4968825
4968866
4968907
2751432
4968999
4968770
1717019
4968901
4968647
4968719
4968826
4968868
4968908
2779061
4969000
4968772
1773844
4968903
4968648
4968720
4968828
4968871
4968909
2801478
4969001
4968773
1803070
4968910
4968649
4968721
4968829
4968872
4968911
2892109
4969003
4968775
1943411
4972318
4968650
4968722
4968830
4968873
4968915
2926805
4969008
4968776
2000216
63197
4968653
4968726
4968831
4968876
4968924
3009638
4969009
4968777
2035278
76242
4968654
4968730
4968832
4968878
4968925
3041256
4969011
4968778
2059619
658065
4968655
4968732
4968833
4968879
4968937
3041273
4969012
4968780
2130568
42 Hie information needs for environmental hazard includes a list of study characteristics pertaining to the test organism/species, type and level of effects, and use of controls. A
complete list of the information needs is provided in Table A2 of the "Approach Document for Screening Hazard Information for Low-Priority Substances Under TSCA". These
information needs helped guide the development of questions for title/abstract and full-text screening.
XLIII
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***Proposal Draft - Do Not Cite, Quote or Release During the Review***
Table C.6: Off-Topic References Excluded at Title/Abstract Screening for Environmental Hazard
667025
4968656
4968737
4968834
4968880
4968950
3041274
4969013
4968781
2131264
790643
4968657
4968739
4968837
4968881
4968952
3041275
4969021
4968782
2134487
1011466
4968658
4968746
4968838
4968885
4968953
3041276
4969024
4968783
2151588
1328729
4968659
4968747
4968840
4968886
4968954
3041277
4969025
4968787
2157782
1407194
4968664
4968749
4968842
4968900
4968955
3041278
4969028
4968788
2167246
1485580
4968665
4968751
4968843
4968681
4968956
3044744
4969063
4968790
2173286
1485781
4968666
4968759
4968844
4968684
4968960
3075503
4969065
4968791
2174181
1487263
4968668
4968760
4968861
4968687
4968966
3471770
4969066
4968792
2185683
1560732
4968670
4968761
4968862
4968688
4968967
4066803
4969067
4968794
2196835
1618382
4968671
4968763
4969236
4968689
4968972
4168368
4969103
4968795
2202115
1619553
4968673
4968765
4969238
4968690
4968973
4441592
4969104
4968798
2214928
4968706
4968677
4968766
4971840
4968692
4968978
4602514
4969106
4968800
2242026
4968707
4968678
4968767
4972381
4968699
4968985
4663144
4969107
4968803
2303721
4968708
4968710
4812821
4972405
4968700
4968987
4671608
4969114
4968808
2310291
4968709
4968711
4969227
4997055
4968702
4968988
4687157
4969117
4969231
2369609
4968991
4968713
4774369
4999208
4968703
4968990
4733946
4969225
4999209
4968704
4968898
4968645
4968716
4968824
4968865
4968906
2521944
4968997
4968769
1621432
Reference excluded (HERO ID]
| because the reference did NOT present quantitative environmental hazard data
N/A
Table C.7: Screening Questions and Off-Topic References Excluded at Full-Text Screening for Environmental Hazard
Question
Off-topic if answer is:
References excluded (HERO ID)
Does the reference contain information pertaining to a low-
priority substance candidate?
No
4968663
What type of source is this reference?
Review article or book chapter that contains only citations to
primary literature sources
N/A
Is quantitative environmental hazard data presented?
No
N/A
Is this primarily a modeling/simulation study? [Note: select
"No" if experimental verification was included in the study]
Yes
N/A
Is environmental hazard data presented for standard or non-
standard aquatic or terrestrial species (fish, invertebrates,
microorganisms, non-mammalian terrestrial species)?
No
N/A
Is exposure measured for the target substance or is the test
substance a mixture (except for reasonable impurities,
byproducts, and aqueous solutions) or formulated product?
Mixture
N/A
Formulated product
N/A
XLIV
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Table C.7: Screening Questions and Off-Topic References Excluded at Full-Text Screening for Environmental Hazard
Question
Off-topic if answer is:
References excluded (HERO ID)
Does the reference report a duration of exposure?
No
N/A
Does the reference report a negative control that is a vehicle
control or no treatment control?
No
N/A
Does the reference include endpoints in the information
needs?
No
N/A
Table C.8: Data Quality Metrics and Unacceptable References Excluded at Data Quality Evaluation for Environmental Hazard
Question
Unacceptable if:
References excluded (HERO ID)
Metric 1:
Test substance Identity
The test substance identity or description cannot be determined from the information
provided (e.g., nomenclature was unclear, CASRN or structure were not reported,
substance name/ description does not match CASRN).
OR
For mixtures, the components and ratios were not characterized or did not include information
that could result in a reasonable approximation of components.
N/A
Metric 2:
Negative controls
A concurrent negative control group was not included or reported.
N/A
Metric 3:
Experimental system
The experimental system (e.g., static, semi-static, or flow-through regime) was not described.
N/A
Metric 4:
Reporting of concentrations
Test concentrations were not reported.
N/A
Metric 5:
Exposure duration
The duration of exposure was not reported.
OR
The reported exposure duration was not suited to the study type and/or outcome(s) of interest
(e.g., study intended to assess effects on reproduction did not expose organisms for an
acceptable period of time prior to mating).
N/A
Metric 6:
Test Organism characteristics
The test species was not reported.
OR
The test species, life stage, or age was not appropriate for the outcome(s) of interest.
N/A
Metric 7:
Outcome assessment methodology
The outcome assessment methodology was not reported.
N/A
Metric 8:
Reporting of Data
Data presentation was inadequate.
OR
N/A
XLV
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***Proposal Draft - Do Not Cite, Quote or Release During the Review***
Table C.8: Data Quality Metrics and Unacceptable References Excluded at Data Quality Evaluation for Environmental Hazard
Question
Unacceptable if:
References excluded (HERO ID)
Major inconsistencies were present in reporting of results.
C.2.3 Fate
For the screening review of LPS candidate squalane, EPA excluded a total of 384 references when assessing environmental fate. Off-topic fate
references excluded at title/abstract screening are listed in Table C.9, and those excluded at full-text screening are listed in Table C. 10. References
in Table C.l 1 represent unacceptable studies based on specific data quality metrics for fate. Off-topic and unacceptable references are displayed
next to the corresponding exclusion criteria.
Table C.9: Off-Topic References Excluded at Initial Screening for Fate
Reference excluded (HERO ID) because the reference did NOT contain information needs43 relevant to environmental fate
4972485
4969120
4380501
4972368
1053215
4969240
4868784
4972392
4968971
4972493
4968898
4969187
4421767
4972369
1165183
4969241
4879948
4972394
4968979
4972494
4968899
4969190
4439503
4972370
1165926
4969249
4885613
4972395
4968981
4972544
4968901
4969192
4653839
4972371
1176168
4969251
4890402
4972396
4968983
4972545
4968903
4969195
4707510
4972372
1179019
4969254
4968727
4972397
4969019
4972546
4968910
4969202
4711674
4972373
1179132
4969270
4968731
4972398
4969029
4972547
4972318
4969204
4712034
4972374
1180685
4969303
4968736
4972399
4969030
4972548
406362
4969208
4713766
4972375
1180952
4969306
4968738
4972400
4969031
4972549
610671
4969212
4718674
4972376
1207024
4969312
4968741
4972401
4969033
4972550
750416
4969215
4718675
4972379
1553568
4969320
4968742
4972402
4969034
4972551
750417
4969216
4718687
4972382
1559363
4972300
4968743
4972403
4969036
4972552
788234
4969217
4718688
4972383
1589053
4972301
4968744
4972404
4969037
4972553
862320
4969226
4731574
4972384
1643038
4972302
4968745
4972406
4969038
4972604
900107
4969228
4732081
4972385
1956791
4972303
4968748
4972407
4969039
4972605
912592
4969229
4865149
4972386
1958333
4972304
4968750
4972408
4969041
4972606
921506
4969232
4865185
4972387
1964775
4972305
4968752
4972434
4969044
4972607
958237
4969235
4865455
4972389
1964964
4972306
4968753
4972435
4969045
4972608
966159
4969237
4866874
4972390
2286747
4972307
4968754
4972436
4969046
4972609
972251
4969239
4868755
4972391
2339827
4972308
4968755
4972437
4969047
4972610
43 Hie information needs for fate includes a list of study characteristics pertaining to the associated media and exposure pathways, associated processes, and use of controls. A
complete list of the information needs is provided in Table A3 of the "Approach Document for Screening Hazard Information for Low-Priority Substances Under TSCA". These
information needs helped guide the development of questions for title/abstract and full-text screening.
XLVI
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***Proposal Draft - Do Not Cite, Quote or Release During the Review***
Table C.9: Off-Topic References Excluded at Initial Screening for Fate
4972647
4972745
4969086
3012659
2541032
4972309
4968756
4972439
4969049
4972611
4972648
4972746
4969088
3035464
2825185
4972310
4968757
4972440
4969050
4972612
4972649
4999220
4969091
3038753
2831987
4972311
4968809
4972442
4969051
4972613
4972650
4999222
4969101
3044681
2911319
4972313
4968887
4972443
4969053
4972614
4972652
4999223
4969102
3220416
2912000
4972314
4968895
4972444
4969054
4972615
4972653
4999224
4969108
3312184
3005771
4972316
4968920
4972446
4969055
4972616
4972655
4999225
4969109
3340942
4972711
4972321
4968928
4972447
4969056
4972617
4972708
4999226
4969110
3457241
4972712
4972322
4968930
4972448
4969072
4972618
4972709
4999227
4969113
3457694
4972713
4972324
4968932
4972450
4969076
4972619
4972710
4999230
4969115
3459918
4972739
4972325
4968934
4972453
4969079
4972646
4972333
4968941
4969116
3579588
4972740
4972326
4968935
4972454
4969081
4972486
4972361
4968943
4969118
3868028
4972741
4972327
4968936
4972455
4969084
4972487
4972362
4968944
4969119
4186269
4972742
4972329
4968938
4972457
4968970
4972488
4972363
4968946
4972491
4351829
4972743
4972330
4968939
4972459
4972367
4972489
4972364
4968948
4972490
4377995
4972744
4972331
4968940
Reference excluded (HERO ID) because the reference did NOT present quantitative environmental fate data
N/A
Table C.10: Screening Questions and Off-Topic References Excluded at Full-Text Screening for Fate
Question
Off-topic if answer is:
References excluded (HERO ID)
Does the reference contain information pertaining
No
900143
to a low- priority substance candidate?
1560732
2477014
4066803
4968706
4968730
4968761
4968775
4968776
4968825
4968826
4968833
4968838
4968840
4969008
XLVII
-------
***Proposal Draft - Do Not Cite, Quote or Release During the Review***
Table C.10: Screening Questions and Off-Topic References Excluded at Full-Text Screening for Fate
Question
Off-topic if answer is:
References excluded (HERO ID)
4969073
4969214
4972393
4972438
4972441
4972451
4972654
4999221
4999229
4968702
What type of source is this reference?
Review article or book chapter that contains only
N/A
citations to primary literature sources
Is quantitative fate data presented?
No
5016718
Is this primarily a modeling/simulation study?
Yes
2551928
[Note: Select "Yes" only if there is no experimental
2568604
verification]
3014628
3014637
3603188
Table C.11: Data Quality Metrics and Unacceptable References Excluded at Data Quality Evaluation for Fate
Data quality metric
Unacceptable if:
References excluded (HERO ID)
Metric 1:
Test substance identity
The test substance identity or description cannot be determined from the information
provided (e.g., nomenclature was unclear and CASRN or structure were not reported).
OR
For mixtures, the components and ratios were not characterized or did not include
information that could result in a reasonable approximation of components.
N/A
Metric 2:
Study controls
The study did not include or report crucial control groups that consequently made the
study unusable (e.g., no positive control for a biodegradation study reporting 0%
removal).
OR
The vehicle used in the study was likely to unduly influence the study results.
4968666
4968783
5016697
5016726
5016727
Metric 3:
Test substance stability
There were problems with test substance stability, homogeneity, or preparation that had
an impact on concentration or dose estimates and interfered with interpretation of study
results.
N/A
XLVIII
-------
***Proposal Draft - Do Not Cite, Quote or Release During the Review***
Table C.11: Data Quality Metrics and Unacceptable References Excluded at Data Quality Evaluation for Fate
Data quality metric
Unacceptable if:
References excluded (HERO ID)
Metric 4:
Test method suitability
The test method was not reported or not suitable for the test substance.
OR
The test concentrations were not reported.
OR
The reported test concentrations were not measured, and the nominal concentrations
reported greatly exceeded the substances water solubility, which would greatly inhibit
meaningful interpretation of the outcomes.
N/A
Metric 5:
Testing conditions
Testing conditions were not reported, and the omission would likely have a substantial
impact on study results.
OR
Testing conditions were not appropriate for the method (e.g., a biodegradation study at
temperatures that inhibit the microorganisms).
4968783
5016697
Metric 6:
System type and design- partitioning
Equilibrium was not established or reported, preventing meaningful interpretation of
study results.
OR
The system type and design (e.g. static, semi-static, and flow-through; sealed, open)
were not capable of appropriately maintaining substance concentrations, preventing
meaningful interpretation of study results.
N/A
Metric 7:
Test organism-degradation
The test organism, species, or inoculum source were not reported, preventing
meaningful interpretation of the study results.
N/A
Metric 8:
Test organism-partitioning
The test organism information was not reported.
OR
The test organism is not routinely used and would likely prevent meaningful
interpretation of the study results.
N/A
Metric 9:
Outcome assessment methodology
The assessment methodology did not address or report the outcome(s) of interest.
4663144
Metric 10:
Data reporting
Insufficient data were reported to evaluate the outcome of interest or to reasonably infer
an outcome of interest.
OR
The analytical method used was not suitable for detection or quantification of the test
substance.
OR
4663144
5016697
XLIX
-------
***Proposal Draft - Do Not Cite, Quote or Release During the Review***
Table C.11: Data Quality Metrics and Unacceptable References Excluded at Data Quality Evaluation for Fate
Data quality metric
Unacceptable if:
References excluded (HERO ID)
Data indicate that disappearance or transformation of the parent compound was likely
due to some other process.
Metric 11:
Confounding variables
There were sources of variability and uncertainty in the measurements and statistical
techniques or between study groups.
N/A
Metric 12:
Verification or plausibility of results
Reported value was completely inconsistent with reference substance data, related
physical-chemical properties, or otherwise implausible, indicating that a serious study
deficiency exists (identified or not).
4663144
------- |